p21

Summary

Gene Symbol: p21
Description: cyclin dependent kinase inhibitor 1A
Alias: CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1, CDK-interacting protein 1, CDK-interaction protein 1, DNA synthesis inhibitor, cyclin-dependent kinase inhibitor 1A (p21, Cip1), melanoma differentiation associated protein 6, wild-type p53-activated fragment 1
Species: human
Products:     p21

Top Publications

  1. Wilson A, Byun D, Nasser S, Murray L, Ayyanar K, Arango D, et al. HDAC4 promotes growth of colon cancer cells via repression of p21. Mol Biol Cell. 2008;19:4062-75 pubmed publisher
    ..in HCT116 cells induced growth inhibition and apoptosis in vitro, reduced xenograft tumor growth, and increased p21 transcription. Conversely, overexpression of HDAC4 repressed p21 promoter activity...
  2. Fan T, Jiang S, Chung N, Alikhan A, Ni C, Lee C, et al. EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression. Mol Cancer Res. 2011;9:418-29 pubmed publisher
    ..b>p21/CDKN1A is activated upon EZH2 knockdown in a p53-independent manner and contributes substantially to cell cycle ..
  3. Suzuki H, Ito R, Ikeda K, Tamura T. TATA-binding protein (TBP)-like protein is required for p53-dependent transcriptional activation of upstream promoter of p21Waf1/Cip1 gene. J Biol Chem. 2012;287:19792-803 pubmed publisher
    ..TLP stimulated expression of several growth-related genes including p21 (p21(Waf1/Cip1))...
  4. Vincent A, Ren S, Harris L, Devine D, Samant R, Fodstad O, et al. Cytoplasmic translocation of p21 mediates NUPR1-induced chemoresistance: NUPR1 and p21 in chemoresistance. FEBS Lett. 2012;586:3429-34 pubmed publisher
    ..that NUPR1 functions as a transcriptional cofactor for the p300-p53 complex and transcriptionally regulates p21 expression...
  5. Kang M, Yang G, Place R, Charisse K, Epstein Barash H, Manoharan M, et al. Intravesical delivery of small activating RNA formulated into lipid nanoparticles inhibits orthotopic bladder tumor growth. Cancer Res. 2012;72:5069-79 pubmed publisher
    ..are examples of RNAa-based drugs that inhibit cancer cell growth by inducing expression of tumor suppressor p21(WAF1/CIP1) (p21)...
  6. Chen J, Li J, Han Q, Sun Z, Wang J, Wang S, et al. Enhancer of zeste homolog 2 is overexpressed and contributes to epigenetic inactivation of p21 and phosphatase and tensin homolog in B-cell acute lymphoblastic leukemia. Exp Biol Med (Maywood). 2012;237:1110-6 pubmed
    ..was significantly upregulated in Nalm-6 cells and this was associated with the silencing of tumor suppressor genes p21, p53 and phosphatase and tensin homolog (PTEN)...
  7. Dai M, Al Odaini A, Arakelian A, Rabbani S, Ali S, Lebrun J. A novel function for p21Cip1 and acetyltransferase p/CAF as critical transcriptional regulators of TGF?-mediated breast cancer cell migration and invasion. Breast Cancer Res. 2012;14:R127 pubmed publisher
    ..Here we investigated the role of p21Cip1 (p21), a member of the core cell cycle machinery, in transforming growth factor-beta (TGF?)-mediated breast ..
  8. Zhi X, Zhao D, Wang Z, Zhou Z, Wang C, Chen W, et al. E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation. Cancer Res. 2013;73:385-94 pubmed publisher
    ..Using protein array analysis we found that RNF126 silencing increased cell-cycle dependent kinase inhibitor p21(cip) protein levels in both MDA-MB-231 and PC3...
  9. Kim B, Lee H, Lee J, Choi C, Kim D, Lee J, et al. Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment. EMBO J. 2012;31:4289-303 pubmed publisher
    Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses...

More Information

Publications192 found, 100 shown here

  1. Wang N, Wang S, Zhang Q, Lu Y, Wei H, Li W, et al. Association of p21 SNPs and risk of cervical cancer among Chinese women. BMC Cancer. 2012;12:589 pubmed publisher
    The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results...
  2. Yamada K, Ono M, Perkins N, Rocha S, Lamond A. Identification and functional characterization of FMN2, a regulator of the cyclin-dependent kinase inhibitor p21. Mol Cell. 2013;49:922-33 pubmed publisher
    ..HDM2, resulting, inter alia, in increased transcription and expression of the cyclin-dependent kinase inhibitor p21 and consequent cell-cycle arrest...
  3. Yano M, Ohkoshi S, Aoki Y, Takahashi H, Kurita S, Yamazaki K, et al. Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression. Liver Int. 2013;33:1218-29 pubmed publisher
    ..Cyclin-dependent kinase inhibitor p21 (Cip1/WAF1), known as a tumour-suppressor gene, has been reported to have paradoxical function, that is, acting as an ..
  4. Seward S, Semaan A, Qazi A, Gruzdyn O, Chamala S, Bryant C, et al. EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53. Cancer Lett. 2013;336:53-60 pubmed publisher
    ..Further, silencing of EZH2 resulted in re-expression of p21(waf1/cip1) and down-regulation of mutant p53. Finally, EZH2 knockdown contributed to attenuated EOC growth in SCID mice.
  5. Garcia Fernandez R, Garcia Palencia P, Suarez C, Sanchez M, Gil Gomez G, Sanchez B, et al. Cooperative role between p21cip1/waf1 and p27kip1 in premature senescence in glandular proliferative lesions in mice. Histol Histopathol. 2014;29:397-406 pubmed publisher
    ..Cellular senescence has been considered a novel target for cancer therapy. 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...
  6. Allouch A, David A, Amie S, Lahouassa H, Chartier L, Margottin Goguet F, et al. p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway. Proc Natl Acad Sci U S A. 2013;110:E3997-4006 pubmed publisher
    ..We have previously shown that the cyclin-dependent kinase inhibitor p21 inhibits the replication of HIV-1 and other primate lentiviruses in human monocyte-derived macrophages by impairing ..
  7. Wang Z, Sturgis E, Zhang F, Lei D, Liu Z, Xu L, et al. Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck. Mol Cancer. 2012;11:17 pubmed publisher
    Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies...
  8. Dunlop M, Dobbins S, Farrington S, Jones A, Palles C, Whiffin N, et al. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat Genet. 2012;44:770-6 pubmed publisher
    ..2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. ..
  9. Ferrandiz N, Caraballo J, García Gutiérrez L, Devgan V, Rodríguez Paredes M, Lafita M, et al. p21 as a transcriptional co-repressor of S-phase and mitotic control genes. PLoS ONE. 2012;7:e37759 pubmed publisher
    It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems...
  10. O Brien C, Kreso A, Ryan P, Hermans K, Gibson L, Wang Y, et al. ID1 and ID3 regulate the self-renewal capacity of human colon cancer-initiating cells through p21. Cancer Cell. 2012;21:777-92 pubmed publisher
    ..colon cancer-initiating cell (CC-IC) self-renewal through cell-cycle restriction driven by the cell-cycle inhibitor p21. Regulation of p21 by ID1 and ID3 is a central mechanism preventing the accumulation of excess DNA damage and ..
  11. Yoon M, Mitrea D, Ou L, Kriwacki R. Cell cycle regulation by the intrinsically disordered proteins p21 and p27. Biochem Soc Trans. 2012;40:981-8 pubmed
    ..In the present paper, we review disorder-mediated cell cycle regulation by two intrinsically disordered proteins, p21 and p27...
  12. Esteras N, Alquezar C, Bermejo Pareja F, Bialopiotrowicz E, Wojda U, Martin Requero A. Downregulation of extracellular signal-regulated kinase 1/2 activity by calmodulin KII modulates p21Cip1 levels and survival of immortalized lymphocytes from Alzheimer's disease patients. Neurobiol Aging. 2013;34:1090-100 pubmed publisher
    ..cell lines showed downregulation of extracellular signal-regulated kinase (ERK)1/2 activity and elevated content of p21 compared with control cells...
  13. Bai J, Chen J, Ma M, Cai M, Xu F, Wang G, et al. Inhibiting enhancer of zeste homolog 2 promotes cellular senescence in gastric cancer cells SGC-7901 by activation of p21 and p16. DNA Cell Biol. 2014;33:337-44 pubmed publisher
    ..To prove that EZH2 expression contributes substantially to the change of key cell cycle regulators, we showed that p21 and p16 were activated to a certain extent upon EZH2 depletion and activation of p21 was in a p53-independent ..
  14. Aravinthan A, Mells G, Allison M, Leathart J, Kotronen A, Yki Jarvinen H, et al. Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease. Cell Cycle. 2014;13:1489-94 pubmed publisher
    ..Previous studies have demonstrated an association between hepatocyte p21 expression and fibrosis stage in NAFLD...
  15. Wilson A, Byun D, Popova N, Murray L, L Italien K, Sowa Y, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem. 2006;281:13548-58 pubmed
    ..its effect on cell growth, overexpression of HDAC3 and other Class I HDACs inhibited basal and butyrate-induced p21 transcription in a Sp1/Sp3-dependent manner, whereas silencing of HDAC3 stimulated p21 promoter activity and ..
  16. Driver K, Song H, Lesueur F, Ahmed S, Barbosa Morais N, Tyrer J, et al. Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population. Carcinogenesis. 2008;29:333-41 pubmed publisher
    ..010, P-trend = 0.048). Further large-scale studies are needed to confirm these results. ..
  17. Carujo S, Estanyol J, Ejarque A, Agell N, Bachs O, Pujol M. Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity. Oncogene. 2006;25:4033-42 pubmed
    ..All these results suggest that GAPDH might be involved in cell cycle regulation by modulating cyclin B-cdk1 activity. ..
  18. Weiss R, Randour C. Attenuation of matrix protein secretion by antisense oligodeoxynucleotides to the cyclin kinase inhibitor p21(Waf1/Cip1). Atherosclerosis. 2002;161:105-12 pubmed
    ..Using an antisense oligodeoxynucleotide to the CKI p21(Waf1/Cip1), developed in our laboratory and shown to specifically inhibit p21(Waf1/Cip1) protein levels, we asked ..
  19. Liu B, Zhang Y, Jin M, Ni Q, Liang X, Ma X, et al. Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk. Mol Carcinog. 2010;49:75-84 pubmed publisher
    ..The study population was composed of 373 CRC cases and 838 controls. Five genetic variants including CCND1 G870A, p21 codon31 C/A, p21 3'UTR C/T, caspase8 IVS12-19G/A, and caspase8 6n del/ins were genotyped...
  20. Chen X, Chi Y, Bloecher A, Aebersold R, Clurman B, Roberts J. N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1). Mol Cell. 2004;16:839-47 pubmed
    Expression of the CDK inhibitor p21(Cip1) is tightly regulated by signals that control cell division...
  21. Bockstaele L, Kooken H, Libert F, Paternot S, Dumont J, De Launoit Y, et al. Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors". Mol Cell Biol. 2006;26:5070-85 pubmed
    ..Thr172-phosphorylated CDK4 was enriched in complexes containing p21 or p27, even at inhibitory levels of p27 that precluded CDK4 activity...
  22. Biankin A, Kench J, Morey A, Lee C, Biankin S, Head D, et al. Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia. Cancer Res. 2001;61:8830-7 pubmed
    ..We examined the protein expression of four functionally related genes, p21(WAF1/CIP1) (CDKN1A), p53, cyclin D1 (CCND1), and DPC4/Smad4 (MADH4), aberrations of which are associated with PC, within 451 ..
  23. Huang L, Seow K, Lee C, Lin Y, Pan H, Chen H. Decreased p21 expression in HPV-18 positive cervical carcinomas. Pathol Oncol Res. 2010;16:81-6 pubmed publisher
    ..to investigate the relationship between different human papillomavirus (HPV) genotypes and the expression of p53, p21 and p27 in cervical carcinomas...
  24. Tsuchiya N, Izumiya M, Ogata Kawata H, Okamoto K, Fujiwara Y, Nakai M, et al. Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res. 2011;71:4628-39 pubmed publisher
    ..miR-22 as a p53 target gene that selectively determines the induction of p53-dependent apoptosis by repressing p21. Combinatorial analyses of the AGO2 immunocomplex and gene expression profiles identified p21 as a direct target of ..
  25. Shats I, Milyavsky M, Tang X, Stambolsky P, Erez N, Brosh R, et al. p53-dependent down-regulation of telomerase is mediated by p21waf1. J Biol Chem. 2004;279:50976-85 pubmed
    ..Knockdown of the key p53 transcriptional target, p21, was sufficient to eliminate the p53-dependent repression of hTERT...
  26. Fillies T, Woltering M, Brandt B, Van Diest J, Werkmeister R, Joos U, et al. Cell cycle regulating proteins p21 and p27 in prognosis of oral squamous cell carcinomas. Oncol Rep. 2007;17:355-9 pubmed
    Cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs), such as p21 and p27, exert a direct control on the cell cycle...
  27. De Siervi A, Marinissen M, Diggs J, Wang X, Pages G, Senderowicz A. Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1. Cancer Res. 2004;64:743-50 pubmed
    ..We have shown previously that perifosine induces p21(waf1/cip1) in a p53-independent fashion and that induction of p21(waf1/cip1) is required for the perifosine-induced cell ..
  28. Herbig U, Jobling W, Chen B, Chen D, Sedivy J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14:501-13 pubmed
    ..damage response factors were assembled in a subset of senescent cells and signaled through ATM to p53, upregulating p21 and causing G1 phase arrest...
  29. Giles K, Daly J, Beveridge D, Thomson A, Voon D, Furneaux H, et al. The 3'-untranslated region of p21WAF1 mRNA is a composite cis-acting sequence bound by RNA-binding proteins from breast cancer cells, including HuR and poly(C)-binding protein. J Biol Chem. 2003;278:2937-46 pubmed
    ..The cyclin-dependent kinase inhibitor p21(WAF1) is a central component of this pathway...
  30. MacPartlin M, Zeng S, Lee H, Stauffer D, Jin Y, Thayer M, et al. p300 regulates p63 transcriptional activity. J Biol Chem. 2005;280:30604-10 pubmed
    ..p300, but not its acetylase-defective mutant AT2, stimulated p63gamma-dependent transcription and induction of p21 in cells, consequently leading to G1 arrest...
  31. Mousses S, Ozcelik H, Lee P, Malkin D, Bull S, Andrulis I. Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer. Hum Mol Genet. 1995;4:1089-92 pubmed
    Several groups have recently isolated and characterized an inhibitor of cyclin-dependent kinases, p21CIP1/WAF1 which is transcriptionally induced by wild-type but not mutant p53...
  32. Mandal S, Davie J. Estrogen regulated expression of the p21 Waf1/Cip1 gene in estrogen receptor positive human breast cancer cells. J Cell Physiol. 2010;224:28-32 pubmed publisher
    The cyclin-dependent kinase inhibitor protein p21(Waf1/Cip1) is a potent tumor suppressor. Here, we demonstrate that estradiol regulates the p21(Waf1/Cip1) gene...
  33. Waggoner S, Johannes G, Liebhaber S. Depletion of the poly(C)-binding proteins alphaCP1 and alphaCP2 from K562 cells leads to p53-independent induction of cyclin-dependent kinase inhibitor (CDKN1A) and G1 arrest. J Biol Chem. 2009;284:9039-49 pubmed publisher
    ..Targeted analysis of genes involved in cell cycle control revealed a marked increase in p21(WAF) mRNA and protein...
  34. Wu M, Chen M, Wu D. Influences of lifestyle habits and p53 codon 72 and p21 codon 31 polymorphisms on gastric cancer risk in Taiwan. Cancer Lett. 2004;205:61-8 pubmed
    Influences of lifestyle habits and p53 codon 72 and p21 codon 31 polymorphisms on the risk for developing primary gastric cancer were examined in 89 gastric adenocarcinoma cases (51 males, 38 females) and 192 controls (106 males, 86 ..
  35. Staalesen V, Knappskog S, Chrisanthar R, Nordgard S, Løkkevik E, Anker G, et al. The novel p21 polymorphism p21G251A is associated with locally advanced breast cancer. Clin Cancer Res. 2006;12:6000-4 pubmed
    b>p21 is a main effector of growth arrest induced by p53. In addition, a second transcript from the same gene (p21B) has been linked to apoptosis...
  36. Lazzarini R, Moretti S, Orecchia S, Betta P, Procopio A, Catalano A. Enhanced antitumor therapy by inhibition of p21waf1 in human malignant mesothelioma. Clin Cancer Res. 2008;14:5099-107 pubmed publisher
    The p21 cyclin-dependent kinase inhibitor was frequently expressed in human malignant pleural mesothelioma (MPM) tissues as well as cell lines...
  37. Wang Y, Fisher J, Mathew R, Ou L, Otieno S, Sublet J, et al. Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21. Nat Chem Biol. 2011;7:214-21 pubmed publisher
    ..the physical basis of IDP binding diversity and report here that the cyclin-dependent kinase (Cdk) inhibitor p21(Cip1) adaptively binds to and inhibits the various Cdk-cyclin complexes that regulate eukaryotic cell division...
  38. Tsai F, Lin H, Chen W, Tsai C, Tsai S. A codon 31ser-arg polymorphism of the WAF-1/CIP-1/p21/tumour suppressor gene in Chinese primary open-angle glaucoma. Acta Ophthalmol Scand. 2004;82:76-80 pubmed
    ..death, and one of its primary regulatory steps is the activation of the tumour suppressor protein p53, of which p21 is an effector protein...
  39. Pardali K, Kowanetz M, Heldin C, Moustakas A. Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21(WAF1/Cip1). J Cell Physiol. 2005;204:260-72 pubmed
    ..TGF-beta) inhibits epithelial cell growth, in part via transcriptional induction of the cell cycle inhibitor p21(WAF1/Cip1) (p21)...
  40. Choi B, Kim C, Bae Y, Lim Y, Lee Y, Shin S. p21 Waf1/Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response-1 expression. Cancer Res. 2008;68:1369-77 pubmed publisher
    ..proliferation in part by suppressing cyclin D1 and inducing expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1)...
  41. Hill R, Bodzak E, Blough M, Lee P. p53 Binding to the p21 promoter is dependent on the nature of DNA damage. Cell Cycle. 2008;7:2535-43 pubmed
    ..How p53 dictates cell fate is unclear. As a major transcriptional target of p53 in response to cellular stress, p21 is a key component in cell cycle control and apoptosis, directing an anti-apoptotic response following DNA damage...
  42. Holm H, Gudbjartsson D, Arnar D, Thorleifsson G, Thorgeirsson G, Stefansdottir H, et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet. 2010;42:117-22 pubmed publisher
    ..00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval. ..
  43. Kashiwagi M, Ohba M, Watanabe H, Ishino K, Kasahara K, Sanai Y, et al. PKCeta associates with cyclin E/cdk2/p21 complex, phosphorylates p21 and inhibits cdk2 kinase in keratinocytes. Oncogene. 2000;19:6334-41 pubmed
    ..We provide here another function of PKC, namely, regulating cell cycle by interaction with the cyclin E/cdk2/p21 complex...
  44. Alt J, Gladden A, Diehl J. p21(Cip1) Promotes cyclin D1 nuclear accumulation via direct inhibition of nuclear export. J Biol Chem. 2002;277:8517-23 pubmed
    There is increasing evidence that p21(Cip1) and p27(Kip1) are requisite positive regulators of cyclin D1.CDK4 assembly and nuclear accumulation...
  45. Lagger G, Doetzlhofer A, Schuettengruber B, Haidweger E, Simboeck E, Tischler J, et al. The tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene. Mol Cell Biol. 2003;23:2669-79 pubmed
    The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation...
  46. Lai K, Chen W, Jeng L, Li S, Chou M, Tsai F. Association of genetic polymorphisms of MK, IL-4, p16, p21, p53 genes and human gastric cancer in Taiwan. Eur J Surg Oncol. 2005;31:1135-40 pubmed
    ..gastric cancer risk and clinical-pathological factors associated with genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes...
  47. Chen X, Barton L, Chi Y, Clurman B, Roberts J. Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome. Mol Cell. 2007;26:843-52 pubmed
    The cell-cycle regulator p21(Cip1) is degraded by proteasomes independently of ubiquitination. We now show that degradation of p21 in vivo does not require the 19S proteasome lid, which contains the ubiquitin-binding subunit...
  48. Johnson G, Sherrington P, Carter A, Lin K, Liloglou T, Field J, et al. A novel type of p53 pathway dysfunction in chronic lymphocytic leukemia resulting from two interacting single nucleotide polymorphisms within the p21 gene. Cancer Res. 2009;69:5210-7 pubmed publisher
    ..and measuring levels of p53 protein and one of its transcriptional targets, the cyclin-dependent kinase inhibitor p21. We have previously identified two abnormal p53/p21 response patterns associated with inactivating mutations of ..
  49. Lee E, Lee M, Camus S, Ghim J, Yang M, Oh W, et al. Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis. EMBO J. 2009;28:2100-13 pubmed publisher
    ..Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent ..
  50. Pang L, Scott M, Hayward R, Mohammed H, Whitelaw C, Smith G, et al. p21(WAF1) is component of a positive feedback loop that maintains the p53 transcriptional program. Cell Cycle. 2011;10:932-50 pubmed
    ..pathway has evolved an intrinsic positive feedback loop that is maintained by the p53-inducible gene product p21(WAF1)...
  51. Poon R, Hunter T. Expression of a novel form of p21Cip1/Waf1 in UV-irradiated and transformed cells. Oncogene. 1998;16:1333-43 pubmed
    The tumor suppressor p53 and its target the CDK inhibitor p21 (Cip1/Waf1) are key components of the cellular response to DNA damage...
  52. Gottwein E, Cullen B. A human herpesvirus microRNA inhibits p21 expression and attenuates p21-mediated cell cycle arrest. J Virol. 2010;84:5229-37 pubmed publisher
    ..Here, we report that cellular mRNAs encoding the cellular cyclin-dependent kinase inhibitor p21, a key inducer of cell cycle arrest, are direct targets for KSHV miR-K1...
  53. Chedid M, Michieli P, Lengel C, Huppi K, Givol D. A single nucleotide substitution at codon 31 (Ser/Arg) defines a polymorphism in a highly conserved region of the p53-inducible gene WAF1/CIP1. Oncogene. 1994;9:3021-4 pubmed
    The recently discovered WAF1/CIP1 gene is a mediator of p53 tumor suppressor activity. To analyse WAF1/CIP1 for possible mutations, polymerase chain reaction (PCR) amplified cDNAs from several tumor cell lines were cloned and sequenced...
  54. Huang S, Shu L, Dilling M, Easton J, Harwood F, Ichijo H, et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell. 2003;11:1491-501 pubmed
    ..Cells expressing wild-type p53 or p21(Cip1)arrest in G1 and remain viable...
  55. Hishida A, Matsuo K, Tajima K, Ogura M, Kagami Y, Taji H, et al. Polymorphisms of p53 Arg72Pro, p73 G4C14-to-A4T14 at exon 2 and p21 Ser31Arg and the risk of non-Hodgkin's lymphoma in Japanese. Leuk Lymphoma. 2004;45:957-64 pubmed
    ..that the polymorphisms in the two p53 family genes (p53 Arg72Pro and p73 G4C14-to-A4T14 at exon 2 (G4A)) and p21 Ser31Arg polymorphism might modulate the risk of non-Hodgkin's lymphoma, and conducted a hospital-based prevalent ..
  56. Morton J, Jamieson N, Karim S, Athineos D, Ridgway R, Nixon C, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology. 2010;139:586-97, 597.e1-6 pubmed publisher
    ..Mechanistically, this was associated with decreased p53/p21-dependent growth arrest...
  57. Kibel A, Suarez B, Belani J, Oh J, Webster R, Brophy Ebbers M, et al. CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma. Cancer Res. 2003;63:2033-6 pubmed
    ..Herein, we examined single nucleotide polymorphic variants in the 3'-untranslated region of CDKN1A (p21(cip1)) and in codon 109 of CDKN1B (p27(kip1)) for association with advanced prostate cancer in a European-American ..
  58. Gomes C, Drummond S, Guimarães A, Andrade C, Mesquita R, Gomez R. P21/ WAF1 and cyclin D1 variants and oral squamous cell carcinoma. J Oral Pathol Med. 2008;37:151-6 pubmed publisher
    ..We evaluated a possible association between CCND1 A870G and P21/WAF1 C98A polymorphisms and OSCC, as well as the impact of the genotypes on protein immunoexpression...
  59. Kim K, Sung Y, Kang C, Choi C, Kang C, Bae S. A regulatory SNP at position -899 in CDKN1A is associated with systemic lupus erythematosus and lupus nephritis. Genes Immun. 2009;10:482-6 pubmed publisher
    The CDKN1A gene encoding a cell cycle inhibitor, p21(WAF1/CIP1), is located in the systemic lupus erythematosus (SLE) susceptibility locus on chromosome 6p21.2. Decreased cellular levels of p21 are associated with SLE...
  60. Roh J, Kim B, Lee C, Kim J, Chung H, Kim J, et al. P53 codon 72 and p21 codon 31 polymorphisms and susceptibility to cervical adenocarcinoma in Korean women. Oncol Res. 2010;18:453-9 pubmed
    The aims of this study were to evaluate the genotype frequencies of p53 codon 72 and p21 codon 31 in cervical adenocarcinoma patients and controls, and the association between the specific genotype or genotype combination of these ..
  61. Avkin S, Sevilya Z, Toube L, Geacintov N, Chaney S, Oren M, et al. p53 and p21 regulate error-prone DNA repair to yield a lower mutation load. Mol Cell. 2006;22:407-13 pubmed
    ..We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency...
  62. Oh Y, Chun K, Park B, Choi J, Lee S. Regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 by protein kinase Cdelta-mediated phosphorylation. Apoptosis. 2007;12:1339-47 pubmed
    Cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1(-/-))-null mice have an increased incidence of tumor formation. Here, we demonstrate that p21(WAF1/CIP1) is unstable in HeLa cells treated with siRNA duplexes that target PKCdelta...
  63. Winters Z, Leek R, Bradburn M, Norbury C, Harris A. Cytoplasmic p21WAF1/CIP1 expression is correlated with HER-2/ neu in breast cancer and is an independent predictor of prognosis. Breast Cancer Res. 2003;5:R242-9 pubmed
    ..05), suggesting an inverse relationship between nuclear p21WAF1/CIP1 and HER-2. This study highlights a new pathway by which HER-2 may modify cancer behaviour...
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    ..The results indicate that Mitf-mediated activation of p21Cip1 expression and consequent hypophosphorylation of Rb1 will contribute to cell cycle exit and activation of the ..
  65. Gravina S, Lescai F, Hurteau G, Brock G, Saramaki A, Salvioli S, et al. Identification of single nucleotide polymorphisms in the p21 (CDKN1A) gene and correlations with longevity in the Italian population. Aging (Albany NY). 2009;1:470-80 pubmed
    ..We have investigated possible associations between longevity and Single Nucleotide Polymorphisms (SNPs) in the p21 (CDKN1A) gene, a stress-inducible senescence-associated cell cycle inhibitor, expression of which upregulates genes ..
  66. Zhan J, Easton J, Huang S, Mishra A, Xiao L, Lacy E, et al. Negative regulation of ASK1 by p21Cip1 involves a small domain that includes Serine 98 that is phosphorylated by ASK1 in vivo. Mol Cell Biol. 2007;27:3530-41 pubmed
    The cyclin-dependent kinase inhibitor p21(Cip1) regulates multiple cellular functions and protects cells from genotoxic and other cellular stresses...
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    Although a major effect of p21, a cyclin-dependent kinase inhibitor, is considered to be exerted during G(1) phase of the cell cycle, p21 gene knock-out studies suggested its involvement in G(2)/M checkpoint as well...
  68. Tsai M, Chen W, Tsai F. Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma. J Clin Lab Anal. 2002;16:146-50 pubmed
    Background p21 (WAF1/CIP1) is a downstream protein from p53 and can arrest the cell cycle at the G1/S phase in response to signal from p53...
  69. Bhattacharya P, Sengupta S. Lack of evidence that proline homozygosity at codon 72 of p53 and rare arginine allele at codon 31 of p21, jointly mediate cervical cancer susceptibility among Indian women. Gynecol Oncol. 2005;99:176-82 pubmed
    ..76; 95% CI = 1.03-13.80; P = 0.04). Significant independent association was evident between the p21 arginine allele (rare allele with frequency of 0...
  70. Hwang Verslues W, Sladek F. Nuclear receptor hepatocyte nuclear factor 4alpha1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter. Mol Endocrinol. 2008;22:78-90 pubmed
    ..factor 4alpha1 (HNF4alpha1) regulates the expression of the human cyclin-dependent kinase inhibitor gene p21/WAF1 (CDKN1A)...
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    ..elegans and humans by targeting the degradation of the cyclin-dependent kinase (CDK) inhibitors CKI-1 and p21(Cip1), respectively...
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    ..These data suggest that p53-mediated repression of RECQ4 transcription during DNA damage results from the modulation of the promoter occupancy of transcription activators and repressors. ..
  73. Själander A, Birgander R, Rannug A, Alexandrie A, Tornling G, Beckman G. Association between the p21 codon 31 A1 (arg) allele and lung cancer. Hum Hered. 1996;46:221-5 pubmed
    ..In this paper the codon 31 polymorphism of the p53-inducible protein p21 was studied in 144 Swedish lung cancer patients and two different control groups: 95 patients with chronic ..
  74. Orend G, Hunter T, Ruoslahti E. Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells. Oncogene. 1998;16:2575-83 pubmed publisher
    ..This anchorage-dependent cell cycle arrest is linked to increased expression of the p21Cip1 (p21) and p27Kip1 (p27) cyclin-dependent kinase inhibitors...
  75. Asada M, Ohmi K, Delia D, Enosawa S, Suzuki S, Yuo A, et al. Brap2 functions as a cytoplasmic retention protein for p21 during monocyte differentiation. Mol Cell Biol. 2004;24:8236-43 pubmed
    The cell cycle inhibitor p21 plays an important role in monocytic cell differentiation, during which it translocates from the nucleus to cytoplasm...
  76. Amador V, Ge S, Santamaria P, Guardavaccaro D, Pagano M. APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell. 2007;27:462-73 pubmed
    During the G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored...
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    Overexpression of p21(cip1) induces cell cycle arrest. Although this ability has been correlated with its nuclear localization, the evidence is not conclusive...
  78. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown J, et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1998;282:1497-501 pubmed
    ..when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, gamma radiated cells progressed into mitosis and exhibited a ..
  79. Wu M, Wu D, Hsu H, Kao E, Yang C, Lee J. Association between p21 codon 31 polymorphism and esophageal cancer risk in a Taiwanese population. Cancer Lett. 2003;201:175-80 pubmed
    b>P21, which regulates the cell growth cycle, is crucial for normal growth and differentiation. One polymorphism in the p21 codon 31 produces variant proteins with an amino acid change (serine (ser) or arginine (arg))...
  80. Lin D, Barbash O, Kumar K, Weber J, Harper J, Klein Szanto A, et al. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell. 2006;24:355-66 pubmed
    ..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1. ..
  81. Ressiniotis T, Griffiths P, Keers S, Chinnery P, Birch M. A polymorphism at codon 31 of gene p21 is not associated with primary open angle glaucoma in Caucasians. BMC Ophthalmol. 2005;5:5 pubmed
    ..b>p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA ..
  82. Mattia M, Gottifredi V, McKinney K, Prives C. p53-Dependent p21 mRNA elongation is impaired when DNA replication is stalled. Mol Cell Biol. 2007;27:1309-20 pubmed
    ..human cell lines, p53 is impaired in its ability to induce a subset of its key target genes, including p21(WAF1/CIP1)...
  83. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev. 2008;22:2496-506 pubmed publisher
    ..Here we demonstrate that PCNA promotes the ubiquitylation and degradation of the CDK inhibitor p21 in cells irradiated with low dose of ultraviolet (UV) by a similar mechanism...
  84. Chen J, Saha P, Kornbluth S, Dynlacht B, Dutta A. Cyclin-binding motifs are essential for the function of p21CIP1. Mol Cell Biol. 1996;16:4673-82 pubmed
    The cyclin-dependent kinase (Cdk) inhibitor p21 is induced by the tumor suppressor p53 and is required for the G1-S block in cells with DNA damage...
  85. Serrano M, Lin A, McCurrach M, Beach D, Lowe S. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593-602 pubmed
    ..Negation of ras-induced senescence may be relevant during multistep tumorigenesis. ..
  86. Bendjennat M, Boulaire J, Jascur T, Brickner H, Barbier V, Sarasin A, et al. UV irradiation triggers ubiquitin-dependent degradation of p21(WAF1) to promote DNA repair. Cell. 2003;114:599-610 pubmed
    p53-mediated increase in cyclin-dependent kinase inhibitor p21(WAF1) protein is thought to be the major mediator of cell cycle arrest after DNA damage...
  87. Munoz Alonso M, Acosta J, Richard C, Delgado M, Sedivy J, Leon J. p21Cip1 and p27Kip1 induce distinct cell cycle effects and differentiation programs in myeloid leukemia cells. J Biol Chem. 2005;280:18120-9 pubmed
    The cyclin-dependent kinase (Cdk) inhibitors p21(Cip1) and p27(Kip1) have been proposed to exert redundant functions in cell cycle progression and differentiation programs, although nonoverlapping functions have also been described...
  88. Yew T, Chiu F, Tsai C, Chen H, Lee W, Chen Y, et al. Knockdown of p21(Cip1/Waf1) enhances proliferation, the expression of stemness markers, and osteogenic potential in human mesenchymal stem cells. Aging Cell. 2011;10:349-61 pubmed publisher
    ..Further, late-passage MSCs showed increased expression of p21(Cip1/Waf1) (p21), an inhibitor of the cyclin-dependent kinase...
  89. Gulbis J, Kelman Z, Hurwitz J, O Donnell M, Kuriyan J. Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA. Cell. 1996;87:297-306 pubmed
    ..antigen) complexed with a 22 residue peptide derived from the C-terminus of the cell-cycle checkpoint protein p21(WAF1/CIP1) has been determined at 2.6 angstrom resolution...
  90. Cazzalini O, Perucca P, Riva F, Stivala L, Bianchi L, Vannini V, et al. p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition. Cell Cycle. 2003;2:596-603 pubmed
    ..To this end, expression of p21 protein fused to green fluorescent protein (GFP) was induced in HeLa cells...
  91. Rodriguez R, Meuth M. Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress. Mol Biol Cell. 2006;17:402-12 pubmed
    ..This death response is independent of p53 and Chk2. p21-deficient cells, on the other hand, produce a more robust apoptotic response upon Chk1 depletion...
  92. Choi Y, Kang H, Choi J, Jang J, Kim E, Cha S, et al. Comprehensive assessment of P21 polymorphisms and lung cancer risk. J Hum Genet. 2008;53:87-95 pubmed
    The purpose of this study is to comprehensively evaluate potential functional polymorphisms in the P21 gene in relation to the risk of lung cancer...