HCSGD entry for CDKN1A

1. General information

Official gene symbol	CDKN1A
Entrez ID	1026
Gene full name	cyclin-dependent kinase inhibitor 1A (p21, Cip1)
Other gene symbols	CAP20 CDKN1 CIP1 MDA-6 P21 SDI1 WAF1 p21CIP1
Links to Entrez Gene	Links to Entrez Gene

2. Neighbors in the network

3. Gene ontology annotation

GO ID	GO term	Evidence	Category
GO:0000079	Regulation of cyclin-dependent protein serine/threonine kinase activity	TAS	biological_process
GO:0000082	G1/S transition of mitotic cell cycle	IDA TAS	biological_process
GO:0000086	G2/M transition of mitotic cell cycle	IMP	biological_process
GO:0000278	Mitotic cell cycle	TAS	biological_process
GO:0000307	Cyclin-dependent protein kinase holoenzyme complex	IDA	cellular_component
GO:0004861	Cyclin-dependent protein serine/threonine kinase inhibitor activity	IEA TAS	molecular_function
GO:0005515	Protein binding	IPI	molecular_function
GO:0005634	Nucleus	IDA IEA	cellular_component
GO:0005654	Nucleoplasm	TAS	cellular_component
GO:0005829	Cytosol	TAS	cellular_component
GO:0006468	Protein phosphorylation	IDA	biological_process
GO:0006974	Cellular response to DNA damage stimulus	IMP	biological_process
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	IDA TAS	biological_process
GO:0007050	Cell cycle arrest	IDA IEA IMP	biological_process
GO:0007173	Epidermal growth factor receptor signaling pathway	TAS	biological_process
GO:0007265	Ras protein signal transduction	IEP	biological_process
GO:0008152	Metabolic process	IDA	biological_process
GO:0008285	Negative regulation of cell proliferation	IDA IMP	biological_process
GO:0008543	Fibroblast growth factor receptor signaling pathway	TAS	biological_process
GO:0009411	Response to UV	IEA	biological_process
GO:0009636	Response to toxic substance	IEA	biological_process
GO:0010243	Response to organonitrogen compound	IEA	biological_process
GO:0010629	Negative regulation of gene expression	IEA	biological_process
GO:0016310	Phosphorylation	IDA	biological_process
GO:0019912	Cyclin-dependent protein kinase activating kinase activity	IDA	molecular_function
GO:0030308	Negative regulation of cell growth	IDA	biological_process
GO:0030332	Cyclin binding	IEA	molecular_function
GO:0030890	Positive regulation of B cell proliferation	IEA	biological_process
GO:0031100	Organ regeneration	IEA	biological_process
GO:0031668	Cellular response to extracellular stimulus	IMP	biological_process
GO:0032403	Protein complex binding	IEA	molecular_function
GO:0033158	Regulation of protein import into nucleus, translocation	IEA	biological_process
GO:0038095	Fc-epsilon receptor signaling pathway	TAS	biological_process
GO:0042326	Negative regulation of phosphorylation	IDA	biological_process
GO:0042327	Positive regulation of phosphorylation	IDA	biological_process
GO:0042493	Response to drug	IEA	biological_process
GO:0042771	Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IEA	biological_process
GO:0043066	Negative regulation of apoptotic process	IEA	biological_process
GO:0043068	Positive regulation of programmed cell death	IEA	biological_process
GO:0043085	Positive regulation of catalytic activity	IDA	biological_process
GO:0045087	Innate immune response	TAS	biological_process
GO:0045736	Negative regulation of cyclin-dependent protein serine/threonine kinase activity	IEA	biological_process
GO:0045860	Positive regulation of protein kinase activity	IDA	biological_process
GO:0046685	Response to arsenic-containing substance	IEA	biological_process
GO:0046872	Metal ion binding	IEA	molecular_function
GO:0048011	Neurotrophin TRK receptor signaling pathway	TAS	biological_process
GO:0048015	Phosphatidylinositol-mediated signaling	TAS	biological_process
GO:0048146	Positive regulation of fibroblast proliferation	IMP	biological_process
GO:0051412	Response to corticosterone	IEA	biological_process
GO:0055093	Response to hyperoxia	IEA	biological_process
GO:0070557	PCNA-p21 complex	IDA	cellular_component
GO:0071479	Cellular response to ionizing radiation	IMP	biological_process
GO:0071850	Mitotic cell cycle arrest	IEA	biological_process
GO:0090398	Cellular senescence	IMP	biological_process
GO:0090400	Stress-induced premature senescence	TAS	biological_process
GO:0097193	Intrinsic apoptotic signaling pathway	TAS	biological_process
GO:2000278	Regulation of DNA biosynthetic process	IEA	biological_process
GO:2000379	Positive regulation of reactive oxygen species metabolic process	IMP	biological_process

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4. Expression levels in datasets

Meta-analysis result

p-value up	p-value down	FDR up	FDR down
0.0000614452	0.9982071578	0.0210038961	1.0000000000

Individual experiment result
( "-" represent NA in the specific microarray platform )

Data source	Up or down	Log fold change
GSE11954	Up	0.5654861656
GSE13712_SHEAR	Up	0.2178911928
GSE13712_STATIC	Up	0.7755892286
GSE19018	Up	2.4595684927
GSE19899_A1	Up	1.3732806803
GSE19899_A2	Up	2.0793529840
PubMed_21979375_A1	Up	0.7301653163
PubMed_21979375_A2	Up	2.2839903154
GSE35957	Up	1.1357257034
GSE36640	Up	1.1229042733
GSE54402	Down	-0.0861124671
GSE9593	Up	0.2377242356
GSE43922	Up	0.8793286075
GSE24585	Up	1.1295885142
GSE37065	Up	0.3046533120
GSE28863_A1	Up	0.3397486492
GSE28863_A2	Down	-0.0982836596
GSE28863_A3	Up	0.0426099789
GSE28863_A4	Down	-0.0598478458
GSE48662	Up	1.8332440862

5. Regulation relationships with compounds/drugs/microRNAs

Compounds

Not regulated by compounds

Drugs

Not regulated by drugs

MicroRNAs

mirTarBase

MiRNA_name	mirBase ID	miRTarBase ID	Experiment	Support type	References (Pubmed ID)
hsa-miR-10b-5p	MIMAT0000254	MIRT006369	Luciferase reporter assay//Western blot	Functional MTI	21471404
hsa-miR-942-5p	MIMAT0004985	MIRT000574	qRT-PCR//Luciferase reporter assay//Western blot	Non-Functional MTI	20190813
hsa-miR-145-5p	MIMAT0000437	MIRT000575	qRT-PCR//Luciferase reporter assay//Western blot	Non-Functional MTI	20190813
hsa-miR-182-5p	MIMAT0000259	MIRT000576	qRT-PCR//Luciferase reporter assay//Western blot	Non-Functional MTI	20190813
hsa-miR-93-5p	MIMAT0000093	MIRT000577	Luciferase reporter assay//Microarray//Western blot	Functional MTI	18328430
hsa-miR-93-5p	MIMAT0000093	MIRT000577	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	19153141
hsa-miR-93-5p	MIMAT0000093	MIRT000577	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-657	MIMAT0003335	MIRT000578	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-654-3p	MIMAT0004814	MIRT000579	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-639	MIMAT0003309	MIRT000580	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-572	MIMAT0003237	MIRT000581	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-520h	MIMAT0002867	MIRT000582	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-520b	MIMAT0002843	MIRT000583	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-520a-3p	MIMAT0002834	MIRT000584	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-519e-3p	MIMAT0002829	MIRT000585	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-519d-3p	MIMAT0002853	MIRT000586	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-519d-3p	MIMAT0002853	MIRT000586	Luciferase reporter assay//Western blot	Functional MTI	22262409
hsa-miR-519b-3p	MIMAT0002837	MIRT000587	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-515-3p	MIMAT0002827	MIRT000588	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-423-3p	MIMAT0001340	MIRT000589	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-372-3p	MIMAT0000724	MIRT000590	qRT-PCR//Luciferase reporter assay//Western blot//Reporter assay;Other	Functional MTI	18212054
hsa-miR-372-3p	MIMAT0000724	MIRT000590	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-363-3p	MIMAT0000707	MIRT000591	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-345-5p	MIMAT0000772	MIRT000592	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-299-5p	MIMAT0002890	MIRT000593	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-298	MIMAT0004901	MIRT000594	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-28-5p	MIMAT0000085	MIRT000595	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-20b-5p	MIMAT0001413	MIRT000596	qRT-PCR//Luciferase reporter assay//Western blot//Reporter assay;Other	Functional MTI	18212054
hsa-miR-20b-5p	MIMAT0001413	MIRT000596	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-20a-5p	MIMAT0000075	MIRT000597	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-20a-5p	MIMAT0000075	MIRT000597	Luciferase reporter assay//qRT-PCR;Other	Functional MTI	18941111
hsa-miR-20a-5p	MIMAT0000075	MIRT000597	Luciferase reporter assay	Functional MTI	21283765
hsa-miR-208b-3p	MIMAT0004960	MIRT000598	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-208a-3p	MIMAT0000241	MIRT000599	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-17-5p	MIMAT0000070	MIRT000600	qRT-PCR//Luciferase reporter assay//Western blot//Reporter assay	Functional MTI	18212054
hsa-miR-17-5p	MIMAT0000070	MIRT000600	qRT-PCR//Western blot//Northern blot//Luciferase reporter assay	Functional MTI	18493594
hsa-miR-17-5p	MIMAT0000070	MIRT000600	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-17-5p	MIMAT0000070	MIRT000600	Luciferase reporter assay//qRT-PCR;Other	Functional MTI	18941111
hsa-miR-17-5p	MIMAT0000070	MIRT000600	Luciferase reporter assay//Western blot	Functional MTI	20227518
hsa-miR-17-5p	MIMAT0000070	MIRT000600	Luciferase reporter assay	Functional MTI	21283765
hsa-miR-132-3p	MIMAT0000426	MIRT000601	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-125a-5p	MIMAT0000443	MIRT000602	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	Luciferase reporter assay//qRT-PCR	Functional MTI	18676839
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	Luciferase reporter assay//Microarray//Western blot	Functional MTI	18328430
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	19153141
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	18212054
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	qRT-PCR//Luciferase reporter assay//Western blot//Microarray	Functional MTI	20385818
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	Luciferase reporter assay//Microarray//qRT-PCR//Western blot	Functional MTI	19422085
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	Luciferase reporter assay	Functional MTI	20101223
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	Luciferase reporter assay	Functional MTI	21283765
hsa-miR-106b-5p	MIMAT0000680	MIRT000603	Reporter assay;Western blot;qRT-PCR	Functional MTI	20709030
hsa-miR-503-5p	MIMAT0002874	MIRT000642	Luciferase reporter assay	Functional MTI	19956200
hsa-miR-106a-5p	MIMAT0000103	MIRT001223	qRT-PCR//Luciferase reporter assay//Western blot//Reporter assay;Other	Functional MTI	18212054
hsa-miR-106a-5p	MIMAT0000103	MIRT001223	Luciferase reporter assay//Western blot	Functional MTI	19782699
hsa-miR-106a-5p	MIMAT0000103	MIRT001223	qRT-PCR//Luciferase reporter assay//Western blot	Functional MTI	20190813
hsa-miR-106a-5p	MIMAT0000103	MIRT001223	qRT-PCR//Luciferase reporter assay//Western blot//Microarray	Functional MTI	20385818
hsa-miR-519a-3p	MIMAT0002869	MIRT006234	Luciferase reporter assay//qRT-PCR//Western blot	Functional MTI	22262409
hsa-miR-96-5p	MIMAT0000095	MIRT003414	Luciferase reporter assay//Microarray//qRT-PCR//Western blot	Functional MTI	19422085
hsa-miR-302a-3p	MIMAT0000684	MIRT004660	Luciferase reporter assay	Functional MTI	20101223
hsa-miR-146a-5p	MIMAT0000449	MIRT004661	Luciferase reporter assay	Non-Functional MTI	20101223
hsa-miR-146b-5p	MIMAT0002809	MIRT004662	Luciferase reporter assay	Non-Functional MTI	20101223
hsa-miR-519c-3p	MIMAT0002832	MIRT006641	Luciferase reporter assay//qRT-PCR//Western blot	Functional MTI	22262409
hsa-miR-335-5p	MIMAT0000765	MIRT017254	Microarray	Functional MTI (Weak)	18185580
hsa-miR-98-5p	MIMAT0000096	MIRT027507	Microarray	Functional MTI (Weak)	19088304
hsa-let-7f-5p	MIMAT0000067	MIRT032095	qRT-PCR	Functional MTI (Weak)	19956384
hsa-let-7a-5p	MIMAT0000062	MIRT032506	Western blot	Functional MTI	19818775
hsa-miR-1229-3p	MIMAT0005584	MIRT036272	CLASH	Functional MTI (Weak)	23622248
hsa-miR-505-5p	MIMAT0004776	MIRT037948	CLASH	Functional MTI (Weak)	23622248
hsa-miR-1260b	MIMAT0015041	MIRT052713	CLASH	Functional MTI (Weak)	23622248

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mirRecord

No target information from mirRecord

6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 162 abstracts the gene occurs.

PubMed ID of the article	Sentenece the gene occurs
27703600	In the present study, we demonstrated that bone marrow mesenchymal stem cells (BMSCs) of the 3rd passage displayed the senescence-associated phenotypes characterized with increased activity of SA-beta-gal, altered autophagy, and increased G1 cell cycle arrest, ROS production, and expression of p53 and p21Cip1/Waf1 compared with BMSCs of the 1st passage
27703600	Moreover, CH inhibited the production of ROS and expression of p53 and p21Cip1/Waf1 in both cellular senescence models and decreased the percentage of BMSCs in G1 cell cycle in the 3rd passage BMSCs
27329245	In line with this, the expressions of p21CIP1 and p27KIP1 were significantly more upregulated in human non-pathological prostatic glands after ADT than in untreated specimens
27294914	X), 8-OHdG, p16(Ink4a), Rb, p21(Cip1/Waf1) and p53 in senescent Sca-1(+) HSC/HPCs
27294914	Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1(+) HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/beta-catenin signaling pathway, and reduction of DNA damage response, p16(Ink4a)-Rb and p53-p21(Cip1/Waf1) signaling
27126529	RESULTS: Senescence markers p21(CIP1/WAF1), senescence-associated ss-galactosidase (SA-ss-gal), and p16(INK4a) were increased 2-, 8-, and 20-fold (n = 5 to 7; p < 0
27074587	Cellular senescence is observed in CAFs treated with H2O2 as shown by elevated SA-beta-gal activity and p21 (WAF1/Cip1) protein levels
27074587	Reactive oxygen species (ROS) production and p21 (WAF1/Cip1) elevation may account for H2O2-induced CAFs cell cycle arrest in S phase
27043659	TRA2beta4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells
27043659	Overexpression of TRA2beta4 significantly decreased CDKN1A mRNA levels and accelerated cell growth, but the introduction of the mutation in the Sp1-binding sequence completely canceled these effects
26854227	PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b
26809688	We show here that HRSV induces the expression of DNA damage markers and proliferation arrest such as P-TP53, P-ATM, CDKN1A and gammaH2AFX in cultured cells secondary to the production of mitochondrial reactive oxygen species (ROS)
26511486	We observed that short-term (4 weeks) oral MSeA treatment significantly increased expression of P53 and P21Cip1 proteins and senescence-associated-beta-galactosidase staining, and reduced Ki67 cell proliferation index in Pten KO prostate epithelium
26503466	At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static
26292757	We have now analyzed the consequences of eliminating a substantial part of the cell-cycle inhibitory activity in the cell by generating a mouse model, which combines the absence of both p21(Cip1) and p27(Kip1) proteins with the endogenous expression of a Cdk4 R24C mutant insensitive to Ink4 inhibitors
26292757	Interestingly, complete abrogation of p21(Cip1) and p27(Kip1) in Cdk4 R24C mutant mice results in a different phenotype characterized by perinatal death accompanied by general hypoplasia in most tissues
26277387	Whereas p21(CIP1/WAF1) was highest in old G1 and G4 Terc(-/-), telomere shortening and p16(INK4a) expression, also significantly associated with later generation young Terc(-/-), were not further induced in old Terc(-/-) mice
26199387	Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome
26199387	We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21(CIP1/WAF1) and p16(INK4a) by HRS cells might be predictive of the probability of event-free survival (EFS)
26199387	The presence or the lack of the robust expression of p21(CIP1/WAF1) and/or p16(INK4a) defined the prognosis in our series
26199387	CONCLUSIONS: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (ii) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16(INK4a) and p21(CIP1/WAF1) expression
26102294	Previously, we showed that following etoposide (ETO) treatment embryonal carcinoma PA-1 cells undergo a p53-dependent upregulation of OCT4A and p21Cip1 (governing self-renewal and regulating cell cycle inhibition and senescence, respectively)
26102294	PA-1 cells treated with ETO display highly heterogeneous increases in OCT4A and p21Cip1 indicative of dis-adaptation catastrophe
26102294	Silencing OCT4A suppresses p21Cip1, changes cell cycle regulation and subsequently suppresses terminal senescence; p21Cip1-silencing did not affect OCT4A expression or cellular phenotype
25991604	Moreover, the absence of MT1-MMP induces a senescent phenotype characterized by up-regulation of p16(INK4a) and p21(CIP1/WAF) (1), increased activity of senescence-associated beta-galactosidase, generation of a senescence-associated secretory phenotype, and somatotroph axis alterations
25945449	RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level
25945449	Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells
25924011	A significant increase in phosphorylation of gamma-H2AX, a surrogate of DNA double strand breaks, as well as in levels of p53, p21CIP1 and p16INK4A is also detected
25924011	Conversely inhibition of SIRT1 and SIRT2 via siRNA or sirtinol treatment also induced senescence in BJ fibroblasts associated with increased SA-beta-gal activity, gamma-H2AX phosphorylation and p53, p21CIP1 and p16INK4A levels
25766527	In particular, Gas6-treated cells displayed decreased staining for SA-beta-Gal, fewer G1 phase cells, and decreased levels of p16(INK4a) and p21(Cip1) expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes
25766317	DNA-damaging reactive oxygen species (ROS) are a by-product of ionizing radiation that lead to the activation of p53, transcription of p21(cip1/waf1) and, in the case of wild-type TP53 HNSCC cells, cause senescence
25695870	Although much is known about the key players in the implementation of senescence, including the pRb and p53 axes and the cyclin dependent kinase inhibitors p16(INK4a) and p21(CIP1), many details remain unresolved
25695870	At the permissive temperature, where pRb and p53 are functionally compromised by T-Ag, cyclin D-CDK4 complexes are disrupted by the high p16(INK4a) levels and reduced expression of p21(CIP1)
25695870	In cells arrested at the non-permissive temperature, p21(CIP1) promotes reassembly of cyclin D-CDK4 yet pRb is in a hypo-phosphorylated state, consistent with cell cycle arrest
25501220	Gene expression of the p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) signaling pathways in the regulation of hematopoietic stem cell aging by ginsenoside Rg1
25501220	The results showed that Rg1 could effectively delay tert-butyl hydroperoxide (t-BHP)-induced senescence and inhibit gene expression in the p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) signaling pathways in HSCs
25412309	We further demonstrate that PKCeta promotes senescence through its ability to upregulate the expression of the cell cycle inhibitors p21(Cip1) and p27(Kip1) and enhance transcription and secretion of interleukin-6 (IL-6)
25412309	Furthermore, we show that the human polymorphic variant of PKCeta, 374I, that exhibits higher kinase activity in comparison to WT-374V, is also more effective in IL-6 secretion, p21(Cip1) expression and the promotion of senescence, further supporting a role for PKCeta in senescence
25341032	Dysregulation of cell-cycle inhibitor CDKN1A/p21 and activation of senescence-associated beta-galactosidase were detected in the stressed SMG duct cells
25328137	Despite NR2E1 regulating targets like p21(CIP1) or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis
25328137	Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16(INK4a) and direct repression of p21(CIP1)
25228591	Using this approach, we found that withaferin A (WA), an Ayurvedic medicine constituent, was a potent inhibitor of CSC stemness leading to cellular senescence primarily via the induction of p21Cip1 expression
25064843	Phospholipase D2 downregulation induces cellular senescence through a reactive oxygen species-p53-p21Cip1/WAF1 pathway
25064843	Taken together, these results show that PLD2 downregulation causes senescence through the p53-p21(Cip1/WAF1) pathway by stimulating ROS production, which is induced by CK2 inhibition
24981831	The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state
24979747	Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1beta, IL-6 and TNF-alpha, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats
24934810	Furthermore, MYC activation leads to reduced expression of the senescence markers p16(INK4A), p21(CIP1), and H3K9me3-containing heterochromatin foci, and an increased percentage of Ki67(+) tumor cells
24934810	However, these tumors were of smaller size, showed increased expression of p16(INK4A) and p21(CIP1), and reduced number of Ki67(+) cells, indicating that MYC inactivation restores BRAF(V600E)-induced senescence
24721210	The elevated apoptotic background of Gadd45alpha-/- cells is accompanied by higher levels of Ser15-phosphorylated p53 and p21/Waf1 proteins that additionally commit the cells to HDIs-induced apoptosis
24713392	Combining in vivo and in vitro studies, we show that M2 macrophages trigger hepatocyte senescence and enhance alcohol-induced hepatocyte senescence, as indicated by increased beta-galactosidase activity, elevated CDKN1A mRNA expression, and induction of nuclear p21
24626178	The aim of this study is to investigate the association between the variants of CDKN1A, which encodes p21, and disease progression in NAFLD
24626178	To this end, the relation between CDKN1A polymorphism and liver fibrosis was studied in 2 cohorts of biopsy-proven NAFLD patients from UK (n = 323) and Finland (n = 123)
24626178	Despite the influence on fibrosis development, SNPs across CDKN1A did not affect the progression of liver fibrosis
24626178	In conclusion, CDKN1A variant rs762623 is associated with the development but not the propagation of progressive liver disease in NAFLD
24471909	The expression of cell-senescence markers p16(INK4a) and p21(CIP1/WAF1) was also immunohistochemically investigated
24471909	We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16(INK4a) and p21(CIP1/WAF1) were expressed, irrespective of BRAF mutation status
24444656	These changes were accompanied by increased p21/WAF1 expression and decreased Retinoblastoma Ser(780) phosphorylation, indicating that BMS-777607 induces not only polyploidy but also senescence
24403591	The cellular senescence response triggered by Tax is caused by hyperactivated NF-kappaB and mediated by cyclin-dependent kinase inhibitors, p21(CIP1/WAF1) and p27(KIP1)
24361399	Cellular senescence was measured by SA-beta-gal staining and based on the protein expression of p53 and p21(Cip1/WAF1)
24361399	SIGNIFICANCE: These results demonstrate that tamoxifen promotes senescence through a ROS-p53-p21(Cip1/WAF1) dependent pathway by inhibiting CK2 activity in breast cancer and colon cancer cells
24335839	The changes of anti-oxidative activities, senescence-related markers senescence-associated beta-galactosidase (SA-beta-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d 7
24335839	Moreover, the irradiation significantly increased SA-beta-gal staining, reduced CFU-mix forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1(+) HSC/HPCs
24322375	Analysis of expression levels of p53, p21(CIP1), p16(INK4a), p27(KIP1), pRb and E2F1 and genetic knockdown of p21(CIP1) demonstrated an important role of p21(CIP1) in RD-triggered cellular senescence
24322375	CONCLUSIONS: Involvement of the DNA damage response and p21(CIP1) defines a novel mechanism of RD action and indicates that RD could be further developed as a promising anticancer agent for cancer therapy
24198727	Both H(2)O(2) treatment and AdRas12V infection induced senescence in VECs, as assessed by senescence-associated beta-Gal activity and the expression of proteins such as p53 and p21(CIP1)
24177958	However, a comprehensive understanding of the role of c-ABL kinase in p53-dependent transcription of p21(CIP1/WAF1) and ensuing cell fate decision is still obscure
24122992	The cells treated with Doxorubicin (0-500 nm) or vehicle control were analyzed for apoptosis, senescence (SA-beta Galactosidase), and expression of CDKN1A (p21), CDKN1B(p27), CDKN2A (p16), E2F1, vimentin and E-cadherin by immuno-histochemistry and/or Western blot
24052415	Cooperative role between p21cip1/waf1 and p27kip1 in premature senescence in glandular proliferative lesions in mice
24052415	It has also been pointed out that p21(cip1/waf1) and p27(kip1) cyclin-dependent kinase inhibitors (CKIs) play a role in cellular senescence in some tumor types
23957394	This revealed that mutant collagen directly reduced replicative lifespan and increased stress-induced SA-ssGal activity, p16(INK4A) expression, and p21(CIP1) expression
23916530	The retinoblastoma protein (RB) and p53 tumor suppressors are central to the process and the growth arrest is primarily implemented by the cyclin-dependent kinase (CDK) inhibitors, p16INK4a and p21CIP1
23773483	Senescence triggered by DGCR8 loss is accompanied by the upregulation of the cell-cycle inhibitor p21CIP1
23773483	We further show that a subset of senescence-associated miRNAs with the potential to target p21CIP1 is downregulated during DGCR8-mediated senescence
23770676	Amongst them, TGF-beta ligands play a major role by regulating p15(INK4b) and p21(CIP1)
23768371	Coumestrol promoted senescence through the p53-p21(Cip1/WAF1) pathway by inducing reactive oxygen species (ROS) production in MCF-7 and HCT116 cells
23688655	The DSBs were associated with phosphorylation of ATM/ATR, a central signal transducer mediating the DNA damage response, and upregulation of the cyclin-dependent kinase inhibitor p21(CIP1)
23657974	Moreover, the senescence- associated cyclin-dependent kinase inhibitors p16(Ink4A) and p21(Cip1) were induced correlating with activation of the G1/S cell cycle inhibitor retinoblastoma protein and terminal proliferation arrest
23643076	The expressions of senescence-associated genes p16(INK4a);, p19(Arf);, p53, p21(Cip1/Waf1); mRNA were detected by RT-PCR
23643076	Western blotting was performed to analyze the expressions of p16(INK4a); and p21(Cip1/Waf1); proteins
23643076	CONCLUSION: DNA damage and senescence-associated biological changes of Sca-1(+);HSC/HPC can be achieved by X-ray radiation, which may be involved in p16(INK4a);-Rb and p19(Arf);-p53-p21(Cip1/Waf1); signal pathways
23623979	Expression of the senescence markers p21(CIP1/WAF1) and p16(INK4a), and SA-beta-galactosidase activity, were higher in HtrA1+/- MEFs than in HtrA1-/- MEFs
23514618	Gene array qPCR analysis of MIA PaCa-2 cells treated with the lead compound revealed significant dose-dependent modulation of a distinct subset of genes, including strong induction of DNA damage responsive genes CDKN1A, DDIT3, GADD45A/G, and PPM1D, and repression of genes involved in telomere maintenance, including hPOT1 and PARP1
23496142	Transfection of early passage endothelial cells with miR-21 resulted in lower angiogenesis, and less cell proliferation mirrored by up-regulation of p21(CIP1) and down-regulation of CDK2
23438604	Consistently, knockdown of pRB, p21(CIP1), and p16(INK4a), but not p53, suppressed SAHF formation induced by BRG1
23383739	METHODS: After treatment with etoposide, selected biochemical and morphological parameters were examined, including: the activity of senescence-associated ss-galactosidase, SAHF formation, cell cycle progression, the induction of p21Cip1/Waf1/Sdi1 and cyclin D1, DNA strand breaks, the disruption of cell membrane asymmetry/integrity and ultrastructural alterations
23383739	Morphological alterations were nevertheless not directly coupled with other senescence markers including a stable cell cycle arrest, SAHF formation or p21Cip1/Waf1/Sdi1 induction
23272171	DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21(CIP1), the lower cellular secretory program and down-regulation of NF-kappaB and its signaling cascade
23178160	Progestin drives breast cancer growth by inducing p21(CIP1) expression through the assembly of a transcriptional complex among Stat3, progesterone receptor and ErbB-2
23178160	Cell cycle regulator p21(CIP1) has controversial biological effects in breast cancer since in spite of its role as cell cycle inhibitor and promoter of cellular senescence, it also induces cell proliferation and chemoteraphy resistance
23178160	We here explored the molecular mechanisms involved in progestin regulation of p21(CIP1) expression
23178160	We also investigated the biological effects of p21(CIP1) in breast cancer cells
23178160	We found that the synthetic progestin medroxyprogesterone acetate (MPA) upregulates p21(CIP1) protein expression via c-Src, signal transducer and activator of transcription 3 (Stat3) and ErbB-2 phosphorylation
23178160	Notably, we also found that ErbB-2 nuclear function plays a key role in MPA-induction of p21(CIP1) expression
23178160	Interestingly, we determined that progestin drives p21(CIP1) transcriptional activation via a novel nonclassical transcriptional mechanism in which progesterone receptor is recruited along with Stat3 and ErbB-2 to a Stat3 binding site at p21(CIP1) promoter
23178160	Our findings revealed that ErbB-2 functions as a coactivator of Stat3 in progestin induction of p21(CIP1) transcriptional activation
23178160	Furthermore, we demonstrated that blockage of p21(CIP1) expression strongly inhibited in vitro and in vivo progestin-induced breast cancer cell proliferation
23178160	These results further support the hypothesis that according to cell context and type of stimulus, p21(CIP1) is capable of inducing cell cycle progression
23178160	Moreover, we provided evidence that Stat3 and nuclear ErbB-2 are key players in progestin-induced p21(CIP1) regulation
23137536	The four miRNA mimics increased senescent-associated beta-galactosidase (SA-beta-gal) staining, p53 and p21(Cip1/WAF1) expression, and reactive oxygen species (ROS) production
23137536	Therefore, the present results show that miR-186, miR-216b, miR-337-3p, and miR-760 cooperatively promote cellular senescence through the p53-p21(Cip1/WAF1) pathway by CKII downregulation-mediated ROS production in HCT116 cells
23049256	Under the same conditions, LMWP-SOD1 abolished activation of the cell cycle regulator proteins, p53 and p21(Cip1), induced by hydrogen peroxide
23041151	Klotho treatment attenuated renal fibrosis through down-regulation of transforming growth factor-beta signaling as well as reduced cellular senescence through down-regulation of p21-cip1 mRNA levels
22971926	Knockdown of MDH1 in young HDFs (PD 20) and the IMR90 human fibroblast cell line resulted in the appearance of significant cellular senescence features, including senescence-associated beta-galactosidase staining, flattened and enlarged morphology, increased population doubling time, and elevated p16(INK4A) and p21(CIP1) protein levels
22871735	During exposure to these low concentrations of MMC, the cells demonstrated evidence of DNA replication stress manifested by expression of gammaH2AX, p21 (WAF1) and a very low level of EdU incorporation into DNA
22627293	Such drug-induced autophagy occurred as a consequence of DNA damage induction, at least in part dependent on drug-mediated telomere uncapping, through a pathway converging on the cyclin-dependent kinase inhibitor 1A (CDKN1A/p21)
22627293	Such drug-induced autophagy occurred as a consequence of DNA damage induction, at least in part dependent on drug-mediated telomere uncapping, through a pathway converging on the cyclin-dependent kinase inhibitor 1A (CDKN1A/p21)
22627293	Indeed, melanoma cells depleted for CDKN1A did not show evidence of autophagic markers upon exposure to Ant1,5
22611193	Cell cycle quiescence is associated with down-regulation of cyclin D1, up-regulation of the cyclin-dependent kinase inhibitors, p21(cip1
22452900	Senescent PSC highly expressed CDKN1A/p21, mdm2 and interleukin (IL)-6, but displayed low levels of alpha-smooth muscle actin
22359668	Expressions of p16(Ink4a), Rb, p53, and p21(Cip1), which have been associated with cellular senescence, were all reduced in human MSCs by the pharmacological inhibition of LPA signaling
22217266	STAT1 knockdown using RNA interference significantly inhibited the progression of HMC senescence and decreased the elevated expression of p53 and p21(Cip1)
22217266	Our results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21(Cip1) pathway, and that losartan could attenuate HMC senescence by regulating STAT1
22206000	The cyclin dependent kinase inhibitors p21(CIP1/WAF1) and p16(INK4a) govern the G(1)/S cell cycle checkpoint and are essential for determining whether a cell enters into an arrested state
22206000	The homeodomain transcription factor MEOX2 is an important regulator of vascular cell proliferation and is a direct transcriptional activator of both p21(CIP1/WAF1) and p16(INK4a)
22206000	We compared the ability of MEOX1 and MEOX2 to activate p21(CIP1/WAF1) and p16(INK4a) expression and induce endothelial cell cycle arrest
22206000	Our results demonstrate for the first time that MEOX1 regulates the MEOX2 target genes p21(CIP1/WAF1) and p16(INK4a)
22206000	MEOX1 and MEOX2 activate p16(INK4a) in a DNA binding dependent manner, whereas they induce p21(CIP1/WAF1) in a DNA binding independent manner
22194422	Gene analysis demonstrated a significant increase of both the amount and the transcription rates of p16(INK4a) and p21(Cip1) mRNA in OP rats
22194422	The increased p16(INK4a) and p21(Cip1) also caused a significant decrease in the level of phosphorylation of retinoblastoma protein
22194422	The increase of p21(Cip1) was associated with increased acetylation of both histone H3 and H4 and decreased trimethylation of histone H3 lysine-27 at the p21(Cip1) promoter
22194422	In the p21(Cip1) coding region, dimethylation of histone H3 lysine-4 was significantly higher (P <0
22193460	The STAT1 and STAT3 activity and the expression of p53 and p21(Cip1) were increased after Angiotensin II and H(2)O(2) treatment
22146591	BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the p21(CIP1) pathway
22146591	Furthermore, high levels of BAG2 were found to induce p21(CIP1)-dependent senescence and subsequent carcinogenetic arrest, suggesting its possible role as an indirect activator of the p21(CIP1) pathway
21880712	Here, we show that ectopic expression of p16(INK4a) and another cyclin-dependent kinase inhibitor, p21(CIP1/WAF1), induces senescence without a SASP, even though they induced other features of senescence, including a stable growth arrest
21788308	Moreover, that the depletion of RASSF1A induced senescence-associated beta-galactosidase activity and increased p21(Cip1) expression suggests that RASSF1A plays a role in the escape of cellular senescence in normal uveal melanocytes
21746877	We unexpectedly discovered that dysregulated cyclin E impairs normal acinar morphogenesis in vitro, and this is associated with the induction of p21(Cip1), p27(Kip1), and cellular senescence
21703415	Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21(Cip1) and p16(INK4a) expression
21629737	Further, with development of senescence and accumulation of p16inka4a and p21CIP1, NANOG is downregulated in most cells
21572997	Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16(INK4A) and p21(CIP1/WAF1) expression
21572997	DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16(INK4A) and p21(CIP1/WAF1) promoter regions
21572997	Enrichment of EZH2, the key factor that methylates histone H3 lysine 9 and 27 residues, was decreased on the p16(INK4A) and p21(CIP1/WAF1) promoter regions
21572997	Taken together, DNMTs have a critical role in regulating the cellular senescence of hUCB-MSCs through controlling not only the DNA methylation status but also active/inactive histone marks at genomic regions of PcG-targeting miRNAs and p16(INK4A) and p21(CIP1/WAF1) promoter regions
21552325	Paradoxically, expression of Tax in most cells leads to drastic up-regulation of cyclin-dependent kinase inhibitors, p21(CIP1/WAF1) and p27(KIP1), which cause p53-/pRb-independent cellular senescence
21552325	Here we demonstrate that p21(CIP1/WAF1)-/p27(KIP1)-mediated senescence constitutes a checkpoint against IKK/NF-kappaB hyper-activation
21552325	Small hairpin RNA-mediated knockdown indicates that RelA induces this senescence program by acting upstream of the anaphase promoting complex and RelB to stabilize p27(KIP1) protein and p21(CIP1/WAF1) mRNA respectively
21383005	EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression
21383005	EZH2 depletion removes histone deacetylase 1 (HDAC1) from the CDKN1A transcriptional start site and downstream region, enhancing histone 3 acetylation globally and at CDKN1A
21383005	EZH2 depletion removes histone deacetylase 1 (HDAC1) from the CDKN1A transcriptional start site and downstream region, enhancing histone 3 acetylation globally and at CDKN1A
21383005	This results in recruitment of RNA polymerase II, leading to p21/CDKN1A activation
21383005	Depletion of EZH2 synergistically activates p21/CDKN1A expression in combination with the HDAC inhibitor trichostatin A
21319227	This senescence-like response was mediated by intracellular ROS generation, but was not attributed to p53 Ser15 phosphorylative activation and was uncoupled from the p21cip1 axis, which has been shown to mediate Pten loss-induced cellular senescence or oncogene-driven senescence
21317932	LKB1/NUAK1 activation leads to cell cycle arrest at the G(1)/S border by inducing expression of p21/WAF1
21317932	Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter
21223585	These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression
21209109	We have shown recently that Tax can drastically upregulate the expression of p27(Kip1) and p21(CIP1/WAF1) through protein stabilization and mRNA trans-activation and stabilization, respectively
21209109	The Tax-induced surge in p21(CIP1/WAF1) and p27(Kip1) begins in S phase and results in cellular senescence
21113463	Cell transfection with anti-E6 and anti-E7 short interfering RNA moderately reduced the expression of mRNA for CDC25C, GRB2, GTSE1, and PLK1 genes and induced expression of CDKN1A (p21(CIP)) gene mRNA
20959475	Importantly, melanocyte-specific activation of BRAF(V600E) in vivo resulted in the formation of skin nevi expressing Thr(223)/Ser(226)-phosphorylated FOXO4 and elevated p21(cip1)
20652617	Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16(INK)(4)(A), p21(CIP)(1)(/WAF)(1) and p27(KIP)(1)
20585577	Loss of ER expression combined with the accumulation of p21(Cip1) correlated with senescence in these cell lines
20422055	METHODOLOGY/PRINCIPAL FINDINGS: Livers of five children aged three years or less undergoing liver transplantation due to tyrosinemia (n = 1), biliary atresia (n = 2), or fulminant hepatitis (n = 2) were analyzed for senescence associated beta-galactosidase (SA-betagal) activity and p16INK4a, p21cip1 and p53
20422055	Staining for p16(INK4a) and p21(cip1) was positive in the explanted liver of the patient with tyrosinemia, in the hepatocytes, the canals of Hering, cholangioles and interlobular bile ducts
20407016	We further observed that RECK depletion downregulates beta1-integrin activation, which was associated with decreased autophosphorylation of focal adhesion kinase and increased expression of a cyclin-dependent kinase inhibitor p21(CIP1)
20160708	The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta
20117203	We also determined senescent fractions, at various PD (over a wide range of senescent cell frequencies) using candidate senescence markers: Ki67, p21 (CDKN1A), gammaH2AX, SAHF and Sen-beta-Gal either alone or in combination, and compared with those derived from growth curves
20089119	Decrease in these miRNAs correlated with increased transcript levels of some established target genes, especially the cdk inhibitor p21/CDKN1A
20010815	In MEFs, Myc-induced senescence was genetically dependent on the ARF-p53-p21Cip1 and p16INK4a-pRb pathways, p21Cip1 and p16INK4a being selectively induced in Cdk2-/- cells
19855935	The p53-p21(Cip1/WAF1) pathway is necessary for cellular senescence induced by the inhibition of protein kinase CKII in human colon cancer cells
19855935	Increased cellular levels of p53 and p21(Cip1/WAF1) protein occurred with the inhibition of CKII
19855935	CKII inhibition upregulated p53 and p21(Cip1/WAF1) expression at post-transcriptional level and transcription level, respectively
19855935	Taken together, this study shows that the activation of the p53-p21(Cip1/WAF1) pathway acts as a major mediator of cellular senescence induced by CKII inhibition
19850045	Significantly diminished foci numbers coupled with massive senescence/growth arrest and elevated expression of cyclin-dependent kinase inhibitors (CDKIs) p21(CIP1), p27(kip1), and/or p16(ink4a) occurred in RBP2-depleted gastric and cervical cancer cells
19850045	RBP2 depletion-mediated senescence and clonogenic defect were attenuated by inhibiting p21(CIP1) or p27(kip1) expression
19723919	Patient BMI also differentially influences prognosis according to p21 CDKN1A status
19689470	VPA and NaBu activated the transcription of p21(CIP1/WAF1) by increasing the acetylation of histone H3 and H4 and eventually blocked the cell cycle at G2/M phase
19338757	Using p53-/- MEFs, we further suggest that this growth arrest by loss of TARSH is evoked by p53-dependent p21(Cip1) accumulation
19118192	This senescent phenotype recapitulated several salient features of replicative senescence, notably the presence of senescence-associated beta-galactosidase (SA beta-gal) activity, apparently irreparable genomic DNA breaks, and elevation of p21(Cip1), p53, and p16(INK4A) tumor suppressor protein levels
19099650	Morphology, senescence-associated beta-galactosidase (SA-beta-gal) staining and cell cycle analysis were used to evaluate the changes in BMMSCs at cellular level while real-time RT-PCR was used to detect the alterations in senescence related gene expression including p16INK4a, p21Cip1/Waf1, p53 and TGF-beta1
19079133	Cellular senescence and organismal ageing in the absence of p21(CIP1/WAF1) in ku80(-/-) mice
19067655	We have tested this hypothesis in a cohort of preimplantation human renal allograft biopsies ( n = 75) that have been assayed by real-time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1
19048622	The TP53 wild-type tumor showed a strong early induction of senescence-like phenotype with overexpression of SA-beta-gal and p21(CIP1)
18678645	Overexpression or knockdown of CSIG did not influence p21(Cip1) and p16(INK4a) expressions
18462273	Telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) were assessed in pre-implantation biopsies of 54 patients and the association of these and various other clinical parameters with serum creatinine after 1 year was determined
18441278	Cigarette smoke triggers code red: p21CIP1/WAF1/SDI1 switches on danger responses in the lung
18441278	2008;39:7-18) reveals that the cyclin-dependent kinase inhibitor p21CIP1/WAF1/SDI1 (designated hereafter as p21), which has been linked to cell cycle growth arrest due to stress or danger cell responses, may modulate alveolar inflammation and alveolar destruction, and thus enlightens our present understanding of how the lung senses injury due to cigarette smoke and integrates these responses with those that activate inflammatory pathways potentially harmful to the lung
18347191	We assayed the requirement of ATM signaling and p21(CIP1) expression for survival in premature senescent tumor cells using pharmacologic inhibitors and antisense oligonucleotides
18347191	We show that the mechanism of action of this effect is directly via p21(CIP1), which acts downstream of ATM
18347191	CONCLUSIONS: Blocking ATM and/or p21(CIP1) following initial treatment with a low dose of senescence-inducing chemotherapy is a potentially less toxic and highly specific treatment for carcinomas
18239191	The cyclin-dependent kinase inhibitor p21(CIP1/WAF1/SDI1) (p21) is an important inhibitory checkpoint regulator of cell cycle progression in response to oxidative and genotoxic stresses
17721438	Knockdown of BS69 by RNA interference in human primary fibroblasts results in elevated levels of p21Cip1 and the appearance of several senescent markers, including enhanced senescence-associated beta-galactosidase activity and formation of senescence-associated heterochromatin foci
17721438	Importantly, knockdown of either p53 or p21Cip1, but not p16(INK4a) or Rb, allows cells to bypass premature senescence that is induced by BS69 knockdown
17721438	Furthermore, we show that BS69 forms complexes with both p53 and p400, and that BS69 associates with the p21Cip1 promoter through p53
17599058	Genetic cooperation between p21Cip1 and INK4 inhibitors in cellular senescence and tumor suppression
17599058	Some of these proteins, p21(Cip1), p16(INK4a) and p15(INK4b), are coexpressed in response to antiproliferative signals such as cellular senescence resulting in cell-cycle arrest
17599058	To understand the roles of these inhibitors and their synergistic effect, we have characterized the growth properties and senescent behavior of primary cells deficient in p21(Cip1) and expressing an endogenous Cdk4(R24C) (cyclin-dependent kinase) mutant (Cdk4(R24C) knock-in cells) insensitive to INK4 proteins
17599058	Inactivation of both p21(Cip1) and INK4 pathways strongly cooperate in suppressing cellular senescence in vitro
17599058	Moreover, mice double mutant in the INK4 and p21(Cip1) pathways (Cdk4(R24C); p21(Cip1)-null mice) display an increased incidence of specific sarcomas, suggesting a significant cooperation between these two families of cell-cycle inhibitors in senescence responses and tumor suppression in vivo
17532297	Because hMSCs were induced cellular senescence due to long-term culture, FGF-2 decreased the percentage of senescent cells and suppressed G1 cell growth arrest through the suppression of p21(Cip1), p53, and p16(INK4a) mRNA expression levels
17452980	Moreover, depletion of hAda3 by siRNA inhibited endogenous p53 acetylation and accumulation of p21cip1 in response to ectopic p14ARF
17227869	Cdc42GAP-/- mouse embryonic fibroblasts and/or tissues display reduced population doubling, significantly dampened DNA damage repair activity after DNA-damaging agent treatment, accumulated genomic abnormalities, and induction of p53, p16Ink4a, p21Cip1, and senescence-associated beta-galactosidase expressions
17012840	Cells lacking VHR upregulated p21(Cip/Waf1) and downregulated many genes for cell cycle regulators, DNA replication, transcription, and mRNA processing
16951325	Strikingly, late passage T cells overexpressing telomerase accumulated the cyclin-dependent inhibitors p16Ink4a and p21Cip1 that have largely been associated with in vitro growth arrest
16951325	We conclude that alternative growth arrest mechanisms such as those mediated by p16Ink4a and p21Cip1 still remained intact and regulated the growth potential of cells independently of their telomere status
16888288	MAIN RESULTS: The patients with emphysema had significantly higher percentages of type II cells positive for p16INK4a and p21CIP1/WAF1/Sdi1 than the asymptomatic smokers and nonsmokers
16888288	They had also significantly higher percentages of endothelial cells positive for p16INK4a than the asymptomatic smokers and nonsmokers, and higher percentages of endothelial cells positive for p21CIP1/WAF1/Sdi1 than the asymptomatic nonsmokers
16821141	In addition, the upregulation of WAF1 and p53 related to biliary apoptosis is found in biliary epithelial cells of PBC, which may be due to cell senescence in response to genotoxic damage such as oxidative stress
16779499	Characterization of the activities of p21Cip1/Waf1 promoter-driven reporter systems during camptothecin-induced senescence-like state of BHK-21 cells
16779499	Transcriptional activation of p21(Cip1/Waf1) gene is known to be one of the key steps in the development of cellular senescence, whereas the elements within the p21(Cip1/Waf1) promoter that regulate the transcriptional activation of p21(Cip1/Waf1) during cellular senescence have not been clearly defined
16779499	Thus, several reporter plasmids were constructed in each of which the gene of green fluorescent protein was placed under the control of a selected fragment of p21(Cip1/Waf1) promoter, and stably transfected into BHK-21 cells
16779499	It was shown that the reporter system constructed with bases -2504 to +406 of the p21(Cip1/Waf1) promoter was very efficient in reflecting the senescence of BHK-21 cells by increased cytosolic fluorescence, and the fluorescence intensity of senescent cells was easily distinguished from that of quiescent cells
16698211	After 40-60 cell population doublings, CEP cultures underwent a terminal growth arrest, had shorter telomeres, up-regulated cell cycle inhibitory proteins, such as p21(CIP1) and stained positive for senescence-associated-beta galactosidase
16288006	Loss of the hSNF5 gene concomitantly inactivates p21CIP/WAF1 and p16INK4a activity associated with replicative senescence in A204 rhabdoid tumor cells
16288006	To compare the replicative senescence caused by hSNF5 in A204 cells to normal cellular senescence, we examined the activation of both p16INK4a and p21CIP/WAF1
16288006	Analogous to normal cellular senescence, both p16INK4a and p21CIP/WAF1 were up-regulated following hSNF5 restoration
16288006	Furthermore, we found that hSNF5 bound the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes
16288006	Instead, p21CIP/WAF1 remained activated by hSNF5 in the absence of high p16INK4a expression, apparently causing the growth arrest in A204
16254068	Compared with early-passage cells, the late-passage HPMC exhibited increased expression of p16INK4a but not of p21Cip1
16243918	Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53
16243918	When compared with native collagen, early passage HUVECs showed increased p53, p21(CIP1) (p21), and p16(INK4a) (p16) mRNA expression after exposure to GC
16234365	Hematopoietic exhaustion appears to be accelerated in the absence of p21(Cip1/Waf1) (p21), a cyclin-dependent kinase inhibitor (CKI) in irradiated hosts
16150936	Of interest, the induction of HSC senescence was associated with a prolonged elevation of p21(Cip1/Waf1), p19(Arf), and p16(Ink4a) mRNA expression, while the expression of p27(Kip1) and p18(Ink4c) mRNA was not increased following TBI
16150936	This suggests that p21(Cip1/Waf1), p19(Arf), and p16(Ink4a) may play an important role in IR-induced senescence in HSCs
15781639	We show here that Tbx2 is overexpressed in melanoma cell lines and that Tbx2 targets histone deacetylase 1 to the p21Cip1 (CDKN1A) initiator
15781639	We show here that Tbx2 is overexpressed in melanoma cell lines and that Tbx2 targets histone deacetylase 1 to the p21Cip1 (CDKN1A) initiator
15781639	Strikingly, expression of an inducible dominant-negative Tbx2 (dnTbx2) leads to displacement of histone deacetylase 1, up-regulation of p21(Cip1) expression, and the induction of replicative senescence in CDKN2A-null B16 melanoma cells
15736438	Checkpoint effectors CDKN1A and Gadd45 correlate with oxidative DNA damage in human prostate carcinoma
15736438	MATERIALS AND METHODS: We examined the expression of CDKN1A and Gadd45 proteins acting on cell cycle checkpoints and DNA repair in PCa relative to the presence of oxidative DNA damage, as measured by the detection of the DNA adduct 8-hydroxy-2-deoxyguanosine (8-OHdG
15736438	RT-PCR was used to evaluate WAF1 and Gadd45 transcripts
15610763	TGF-beta1 induced neither expression of senescence-associated markers nor genes involved in terminal growth arrest, such as senescence-associated beta-galactosidase and cyclin-dependent kinase (cdk) inhibitors p16(Ink4A) and p21(Cip1) but increased p15(Ink4B) protein expression
15333326	The senescence was characterized by a dose- and time-dependent increase in senescence-associated beta-galactosidase activity, senescence-associated changes in cell morphology, an increase in cell size and lysosomal mass, accumulation of lipofuscin, overexpression of p21(CIP1/WAF1/Sdi1) protein, and irreversible growth arrest
15333326	In vivo experiments in Institute for Cancer Research mice showed that inhalation of CS for 2 wk induced increases in senescence-associated beta-galactosidase activity, lipofuscin accumulation, and p21(CIP1/WAF1/Sdi1) protein expression in alveolar epithelial cells
15242773	The induction of HDF senescence was associated with an activation of p53, increased expression of p21Cip1/WAF1, and hypophosphorylation of retinoblastoma protein (Rb), while no changes in the expression of p16Ink4a, p27Kip1, and p14Arf were observed
15149599	Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a)
14729964	BRG1 controls the activity of the retinoblastoma protein via regulation of p21CIP1/WAF1/SDI
14729964	We present evidence that the BRG1-containing complexes regulate the expression of the cdk inhibitor p21(CIP1/WAF1/SDI)
14677632	Real-time imaging of transcriptional activation in live cells reveals rapid up-regulation of the cyclin-dependent kinase inhibitor gene CDKN1A in replicative cellular senescence
14677632	The cyclin-dependent kinase (Cdk) inhibitor p21(CIP1/WAF1) (p21), encoded by the CDKN1A gene, is a critical cell cycle regulator whose expression increases as cells approach senescence
14677632	The cyclin-dependent kinase (Cdk) inhibitor p21(CIP1/WAF1) (p21), encoded by the CDKN1A gene, is a critical cell cycle regulator whose expression increases as cells approach senescence
14677632	We used homologous recombination to generate non-immortalized fibroblast cells with the enhanced yellow fluorescence protein (EYFP) gene knocked into one CDKN1A gene copy, allowing promoter activity to be visualized as fluorescence intensity
14500376	This suggests that IR induces hematopoietic cell senescence in a p53-p21(Cip1/Waf1)-dependent manner, whereas the induction of senescence by BU bypasses the p53-p21(Cip1/Waf1) pathway
12943534	Although it was shown that activation of the senescence programme involves the up-regulation of cell-cycle regulators such as the inhibitors of cyclin-dependent kinases p16INK4A and p21CIP-1, the mechanisms underlying the senescence response remain to be resolved
12877804	METHODS: Using a PI3Ks specific inhibitor, LY294002, cell cycle, apoptosis, proliferation, senescence association beta-galactosidase staining as well as senescence association CKIs, p16(INK4) and p21(Cip1) protein expressions were all measured in the low passages of 2BS cells
12877804	In addition, LY294002 could induce time-course expressions of p16(INK4) and p21(Cip1) in 2BS cell lines
12877804	Two senescence associated CKIs, p16(INK4) and p21(Cip1), might be involved in this senescence phenotype proceeding in 2BS cell lines
12743603	Specific molecular markers such as p21/WAF1, activated caspase-3 and activated Akt were associated with these death modes
12743603	The combination of doxorubicin and Q-VD-OPH caused an increased expression of p21/WAF1 and senescence -associated -beta-galactosidase activity, but did not alter Akt activation
12629205	EGR1-null mouse embryo fibroblasts (MEFs) exhibit decreased expression of p53, p21(Cip1/Waf1), and other p53 "marker" proteins
12414954	At the molecular level, cells infected by HCMV, beside the accumulation of large amounts of the cell cycle regulators p53 and pRb, the latter in its hyperphosphorylated form, display a strong induction of the cyclin-dependent kinase inhibitor (cdki) p16(INK4a), a direct effector of the senescence phenotype in fibroblasts, and a decrease of the cdki p21(CIP1/WAF)
11781834	We find that p53, p21(CIP1) and p15(INK4b) are transiently elevated in HPECs and HUCs at the pre-senescent growth arrest, then return to low proliferating levels at terminal senescence
11781834	Analysis of p53, p21(CIP1), p15(INK4b), p16(INK4a), and p57(KIP2) reveals altered expression in immortalized, non-tumorigenic HPV16 E6 and E7 prostate lines and in tumorigenic prostate cancer cells
11695244	Transient expression of various CDKIs (p15INK4b, p16INK4a and p21CIP1/WAF1) in KHOS cells resulted in growth arrest and the cells failed to enter the S-phase of the cell cycle as shown by a DNA synthesis inhibition assay
11695244	In addition, stable transfection of p21CIP1/WAF1 and p16INK4a genes in two osteosarcoma cell lines (KHOS and U2-OS cells) showed that p21CIP1/WAF1 was able to repress the immortal phenotype in both cell lines, whereas temporary over-expression of p16INK4a reversibly inhibited the cell growth
11551927	The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse epidermal differentiation, senescence, and carcinogenesis
11500132	Prolonged up-regulation of expression of CDKN1A (also known as p21(CIP1/WAF1)) after irradiation was noted by Western blot analysis, again suggesting a similarity to natural senescence
11103932	In contrast to observations in fibroblast, p21Cip1 was not increased at senescence in HMECs
10958672	Irreversible G(1) arrest in senescent human fibroblasts is mediated by two inhibitors of cyclin-dependent kinases (Cdks), p21(Cip1/SDI1/WAF1) and p16(Ink4A)
10832053	Cyclin-dependent kinase inhibitors p16(INK4a), p21(Cip1), and p27(Kip1) are regarded as key effectors of cellular senescence
10537318	This lack of cdk activity and arrest in the G1 phase of the cell cycle is likely attributable to the induction upon senescence of the G1-S cdk/cyclin inhibitors p21 (WAF1/CIP1/Sdi) and p16INK4
10381287	The effect of delivering expression vector plasmids for senescent cell-derived inhibitor SDI-1, which regulates cell proliferation, and its antisense, into the perivascular tissue of injured arteries was investigated in a porcine arterial injury model using a needle injection catheter
10049783	Furthermore, the expression of mRNAs for p21/Waf1/Cip1/Sdi1, IRF-1 and IFN inducible 6-16 was higher in the telomere-reduced cells than in the parental cells
10047459	Two posttranscriptional pathways that regulate p21(Cip1/Waf1/Sdi1) are identified by HPV16-E6 interaction and correlate with life span and cellular senescence
10047459	The p21((Cip1/Waf1/Sdi1)) protein is a cyclin-dependent kinase inhibitor that is induced in normal human fibroblasts (NHF) following DNA damage, following serum stimulation, and at cellular senescence
9704925	The levels of other G1 regulating proteins were also altered in the senescent cells, such as slightly elevated levels of p21/WAF1, and downregulation of Cdk2 and cyclinD3
9512419	Senescent cells have a number of characteristics that distinguish them from cycling or quiescent cells including elevated levels of two cyclin-dependent kinase (Cdk) inhibitors, p16INK4a and p21CIP1 [5-11]
9488478	Immunofluorescence analysis showed that expression of the p53-inducible cyclin/kinase inhibitor p21sdi1/WAF1 was greatly diminished by targeting p53 with either PAb1801 or DO-1 but remained high and, moreover, still p53 dependent in cells expressing SV40 T antigen
9486850	Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts
9486850	Immunoblots of 5-aza-2'-deoxycytidine-treated cells showed a greatly increased expression of p16INK4a protein but no detectable change in the expression of p21CIP1, a gene known to be strongly expressed in senescent normal human fibroblasts
9486850	In two other experimental series, cells of the two LF lines were infected with retroviral constructs encoding either p16INK4a or p21CIP1
9486850	The results show that induction of senescence in immortal LF fibroblasts can occur by different pathways: (a) by demethylation-dependent pathways that induce the expression of p16INK4a; and (b) by demethylation-independent pathways involving the expression of p21CIP1
9486850	The induction of senescence by p16INK4a and p21CIP1 occurred equally in the two human immortal fibroblast lines, which differed in the length of their telomeres and the activity of their telomerase
9440695	Furthermore, activation of transcription from the p21/WAF1 promoter, a key mechanism of p53-mediated growth control, depends on the expression of ING1
8997395	The p53-independent activation of transcription of p21 WAF1/CIP1/SDI1 after acute renal failure
8957006	The absence of p21Cip1/WAF1 alters keratinocyte growth and differentiation and promotes ras-tumor progression
8853893	The other two were novel E2F complexes that contained the cyclin-dependent kinase inhibitor p21 (cip1/WAF1/Sdi1/CAP20/PIC1) complexed with Rb/CDK2/cyclin E or with the Rb-related p107/CDK2/ cyclin D
8706802	Studies demonstrating the complexity of regulation and action of the growth inhibitory gene SDI1
8706802	The identification of the DNA synthesis inhibitory gene SDI1 by investigators studying cell senescence, tumor suppression, cell cycle control and differentiation suggest a key regulatory role for this gene
8706802	The data demonstrate that SDI1 is an important downstream effector of p53, but here we report that it can also cause inhibition of DNA synthesis in several immortal human cell lines, independent of p53 or Rb status
7615495	The C-terminal region of p21SDI1/WAF1/CIP1 is involved in proliferating cell nuclear antigen binding but does not appear to be required for growth inhibition
7615495	The cyclin-dependent kinase (Cdk) inhibitor p21SDI1/WAF1/CIP1 has been found to be involved in cell senescence, cell cycle arrest, and differentiation
7603034	Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin
7603034	A newly discovered senescent cell-derived inhibitor (SDI1) plays a critical role in the cell cycle, so we evaluated the effect of 9NC on the expression of the SDI1 gene
7603034	EXPERIMENTAL DESIGN: The effects of 9NC on HepG2 cells were evaluated by monitoring DNA synthesis, morphologic and ultrastructural changes of cells, and perturbation in the cell cycle and by assessing the levels of p53 protein and SDI1 mRNA
7603034	In contrast to untreated, logarithmically grown HepG2 cells, 9NC-treated cells arrested at the G2-phase of the cell cycle and contained increased levels of SDI1 mRNA
7603034	Kinetic studies revealed gradual increases in SDI1 mRNA synthesis
7603034	CONCLUSIONS: Induction of SDI1 mRNA by 9NC represents the first documentation that the SDI1 gene can be overexpressed in the G2-phase of the cell cycle and provides a valuable cell culture system to dissect the events controlling the G2 checkpoint
7538902	Mutant p53 rescues human diploid cells from senescence without inhibiting the induction of SDI1/WAF1
7538902	Although the cyclin-dependent kinase inhibitor p21SDI1 (WAF1/CIP1) has been proposed as the mediator of p53-induced cell cycle arrest following DNA damage, several stimuli now appear to induce SDI1 independent of p53 function
7538902	We have examined the behavior of p53 and SDI1 in an isogeneic model by manipulating p53 status in normal diploid human fibroblasts using an amphotropic retroviral vector
7538902	Following DNA strand break damage induced by bleomycin, both SDI1 induction and G1-S cell cycle arrest are p53 dependent, consistent with SDI1 being the key mediator
7538902	In contrast, in cellular senescence (and following UV irradiation), induction of SDI1 occurs independent of p53 function yet growth arrest is still p53 dependent
7538902	We conclude (a) that redundant pathways exist for induction of SDI1, but that (b) SDI1, while perhaps necessary, is not sufficient for inhibition of cell cycle progression, requiring the cooperation of an additional factor (possibly another cyclin-dependent kinase inhibitor) whose expression, at least in the case of senescence, is strictly p53 dependent
3169139	A potent DNA synthesis inhibitor expressed by the immortal cell line SUSM-1
3169139	We have previously reported the production of DNA synthesis inhibitor proteins by both quiescent and senescent human diploid fibroblasts
3169139	One hypothesis is that the DNA synthesis inhibitor protein(s) of senescent cells plays a role in determining the finite in vitro life span of normal cells

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HCSGD entry for CDKN1A

1. General information

2. Neighbors in the network

3. Gene ontology annotation

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Individual experiment result ( "-" represent NA in the specific microarray platform )

( "-" represent NA in the specific microarray platform )

5. Regulation relationships with compounds/drugs/microRNAs

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6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 162 abstracts the gene occurs.

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Sentenece the gene occurs

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( "-" represent NA in the specific microarray platform )