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. 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. 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...
  3. 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
    ..examples of RNAa-based drugs that inhibit cancer cell growth by inducing expression of tumor suppressor p21(WAF1/CIP1) (p21)...
  4. 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)...
  5. 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 TGFβ-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 (TGFβ)-mediated breast ..
  6. 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...
  7. 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...
  8. 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...
  9. 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 ..
  10. 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.

Detail Information

Publications62

  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. 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...
  3. 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
    ..examples of RNAa-based drugs that inhibit cancer cell growth by inducing expression of tumor suppressor p21(WAF1/CIP1) (p21)...
  4. 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)...
  5. 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 TGFβ-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 (TGFβ)-mediated breast ..
  6. 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...
  7. 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...
  8. 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...
  9. 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 ..
  10. 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.
  11. 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...
  12. 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 ..
  13. 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))...
  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. 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. ..
  16. 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...
  17. 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...
  18. 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 ..
  19. 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...
  20. 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...
  21. 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 ..
  22. Chao C, Chen C, Cheng P, Shih J, Tsou A, Lee Y. DDX3, a DEAD box RNA helicase with tumor growth-suppressive property and transcriptional regulation activity of the p21waf1/cip1 promoter, is a candidate tumor suppressor. Cancer Res. 2006;66:6579-88 pubmed
    ..Additionally, we identified p21(waf1/cip1), a cyclin-dependent kinase inhibitor, as a target gene of DDX3, and the up-regulation of p21(waf1/cip1) expression ..
  23. Azzato E, Driver K, Lesueur F, Shah M, Greenberg D, Easton D, et al. Effects of common germline genetic variation in cell cycle control genes on breast cancer survival: results from a population-based cohort. Breast Cancer Res. 2008;10:R47 pubmed publisher
    ..in 13 genes involved in cell cycle control (CCND1, CCND2, CCND3, CCNE1, CDK2 [p33], CDK4, CDK6, CDKN1A [p21, Cip1], CDKN1B [p27, Kip1], CDKN2A [p16], CDKN2B [p15], CDKN2C [p18], and CDKN2D [p19]) and survival among women ..
  24. Braun F, Bertin Ciftci J, Gallouet A, Millour J, Juin P. Serum-nutrient starvation induces cell death mediated by Bax and Puma that is counteracted by p21 and unmasked by Bcl-x(L) inhibition. PLoS ONE. 2011;6:e23577 pubmed publisher
    The cyclin-dependent kinase inhibitor p21 (p21WAF1/Cip1) is a multifunctional protein known to promote cell cycle arrest and survival in response to p53-dependent and p53 independent stimuli...
  25. Goode E, Fridley B, Vierkant R, Cunningham J, Phelan C, Anderson S, et al. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:935-44 pubmed publisher
    ..These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls. ..
  26. LaBaer J, Garrett M, Stevenson L, Slingerland J, Sandhu C, Chou H, et al. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997;11:847-62 pubmed
    ..In this report we demonstrate that the CDK inhibitors p21(CIP), p27(KIP), and p57(KIP2) all promote the association of cdk4 with the D-type cyclins...
  27. Oliva J, Caino M, Senderowicz A, Kazanietz M. S-Phase-specific activation of PKC alpha induces senescence in non-small cell lung cancer cells. J Biol Chem. 2008;283:5466-76 pubmed
    ..the progression into S phase, an effect mediated by PKC delta-induced up-regulation of the cell cycle inhibitor p21 Cip1. However, PMA treatment in asynchronously growing NSCLC cells leads to accumulation of cells in G2/M...
  28. Garcia Wilson E, Perkins N. p21WAF1/CIP1 regulates the p300 sumoylation motif CRD1 through a C-terminal domain independently of cyclin/CDK binding. Cell Cycle. 2005;4:1113-9 pubmed
    Although best known for its ability to inhibit Cyclin/Cdk complexes and the replication protein PCNA, p21(WAF1/CIP1) is a multifunctional protein that interacts with many cellular binding partners, including a number of transcriptional ..
  29. Besson A, Yong V. Involvement of p21(Waf1/Cip1) in protein kinase C alpha-induced cell cycle progression. Mol Cell Biol. 2000;20:4580-90 pubmed
    ..rapidly altered and increased by PKC alpha activity was the cyclin-cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1)...
  30. Kim W, Kang K, Kim M, Choi K. Induction of p53-independent p21 during ceramide-induced G1 arrest in human hepatocarcinoma cells. Biochem Cell Biol. 2000;78:127-35 pubmed
    ..In this paper, we investigated whether p21, a cdk (cyclin-dependent kinase) inhibitor, is involved in the induction of pRb dephosphorylation during ceramide-..
  31. Devgan V, Mammucari C, Millar S, Brisken C, Dotto G. p21WAF1/Cip1 is a negative transcriptional regulator of Wnt4 expression downstream of Notch1 activation. Genes Dev. 2005;19:1485-95 pubmed
    In keratinocytes, the cyclin/CDK inhibitor p21(WAF1/Cip1) is a direct transcriptional target of Notch1 activation; loss of either the p21 or Notch1 genes expands stem cell populations and facilitates tumor development...
  32. Rossig L, Jadidi A, Urbich C, Badorff C, Zeiher A, Dimmeler S. Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells. Mol Cell Biol. 2001;21:5644-57 pubmed
    ..Here, we demonstrate that Akt phosphorylates the cell cycle inhibitory protein p21(Cip1) at Thr 145 in vitro and in intact cells as shown by in vitro kinase assays, site-directed mutagenesis, and phospho-..
  33. Göhring U, Bersch A, Becker M, Neuhaus W, Schondorf T. p21(waf) correlates with DNA replication but not with prognosis in invasive breast cancer. J Clin Pathol. 2001;54:866-70 pubmed
    b>p21(waf) plays a central role both in the regulation of the cell cycle and in DNA replication. Accordingly, p21(waf) is a putative tumour suppressor...
  34. Popanda O, Edler L, Waas P, Schattenberg T, Butkiewicz D, Muley T, et al. Elevated risk of squamous-cell carcinoma of the lung in heavy smokers carrying the variant alleles of the TP53 Arg72Pro and p21 Ser31Arg polymorphisms. Lung Cancer. 2007;55:25-34 pubmed
    ..We therefore investigated the combined effects of polymorphisms in TP53 (Arg72Pro) and p21/CDKN1A (Ser31Arg) and smoking on lung cancer risk...
  35. Keshava C, Frye B, Wolff M, McCanlies E, Weston A. Waf-1 (p21) and p53 polymorphisms in breast cancer. Cancer Epidemiol Biomarkers Prev. 2002;11:127-30 pubmed
    p53 is a transcription factor for Waf-1/p21, a cyclin-dependent kinase inhibitor. Certain polymorphic variants of Waf-1 and p53 have been evaluated for their association with cancer risk...
  36. Sieburg M, Tripp A, Ma J, Feuer G. Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 tax oncoproteins modulate cell cycle progression and apoptosis. J Virol. 2004;78:10399-409 pubmed
    ..Tax1 markedly activated transcription from the cdk inhibitor p21(cip1/waf1) promoter in comparison to Tax2, suggesting that upregulation of p21(cip1/waf1) may account for the ..
  37. Xia W, Chen J, Zhou X, Sun P, Lee D, Liao Y, et al. Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients. Clin Cancer Res. 2004;10:3815-24 pubmed
    The diversity of biological functions makes p21(Cip1/WAF1) (p21) a controversial marker in predicting the prognosis of breast cancer patients...
  38. Heron Milhavet L, Franckhauser C, Rana V, Berthenet C, Fisher D, Hemmings B, et al. Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding. Mol Cell Biol. 2006;26:8267-80 pubmed
    ..overexpression of Akt2 reduced cyclin A and hindered cell cycle progression in M-G1 with increased nuclear p21. p21 is a major target in the differential effects of Akt isoforms, with endogenous Akt2 and not Akt1 binding p21 ..
  39. Kehn K, Deng L, de La Fuente C, Strouss K, Wu K, Maddukuri A, et al. The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells. Retrovirology. 2004;1:6 pubmed
    ..We have previously shown that Tax upregulates the cell cycle checkpoint proteins p21/waf1 and cyclin D2...
  40. Wang Z, Bhattacharya N, Mixter P, Wei W, Sedivy J, Magnuson N. Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase. Biochim Biophys Acta. 2002;1593:45-55 pubmed
    ..In this study, we have found that amino acid residues 140-147 (RKRRQTSM) at the C-terminal end of p21(Cip1/WAF1), a cyclin-dependent kinase (CDK) inhibitor, constitute an ideal phosphorylation consensus sequence for Pim-1...
  41. Löhr K, Möritz C, Contente A, Dobbelstein M. p21/CDKN1A mediates negative regulation of transcription by p53. J Biol Chem. 2003;278:32507-16 pubmed
    ..Strikingly, when the p53-inducible p21/CDKN1A gene was deleted, p53 no longer repressed any one among 11 genes that it down-regulates otherwise...
  42. Scott M, Ingram A, Ball K. PDK1-dependent activation of atypical PKC leads to degradation of the p21 tumour modifier protein. EMBO J. 2002;21:6771-80 pubmed
    p21(WAF1/CIP1) Contributes to positive and negative growth control on multiple levels. We previously mapped phosphorylation sites within the C-terminal domain of p21 that regulate proliferating cell nuclear antigen binding...
  43. Jones D, Alani R, Munger K. The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2. Genes Dev. 1997;11:2101-11 pubmed
    ..keratinocytes show delayed cellular differentiation and elevated cdk2 kinase activity despite high levels of p21(Cip1) and association of p21(Cip1) with cdk2...
  44. Harima Y, Sawada S, Nagata K, Sougawa M, Ostapenko V, Ohnishi T. Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women. Int J Mol Med. 2001;7:261-4 pubmed
    The WAF1 gene, located on chromosome 6p21.2, has been cloned and identified as a p53 mediator and an inhibitor of G1 cyclin-dependent kinases (CDKs)...
  45. Tu Y, Wu W, Wu T, Cao Z, Wilkins R, Toh B, et al. Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. J Biol Chem. 2007;282:11722-31 pubmed
    ..is accompanied by increases in protein and mRNA levels of the cyclin-dependent kinase (Cdk) inhibitor protein, p21(Waf1/Cip1) (p21). Both p21 induction and cell growth arrest are reversed when CDA1 expression is inhibited...
  46. Lee H, Zeng S, Lu H. UV Induces p21 rapid turnover independently of ubiquitin and Skp2. J Biol Chem. 2006;281:26876-83 pubmed
    ..not high doses, of UV trigger the Skp2-mediated proteasomal degradation of the cyclin-dependent kinase inhibitor p21 in mammalian cells...
  47. Rajaraman P, Wang S, Rothman N, Brown M, Black P, Fine H, et al. Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults. Cancer Epidemiol Biomarkers Prev. 2007;16:1655-61 pubmed
    ..Our results suggest that common variants in the CASP8, CCND1, CCNH, and MDM2 genes may influence brain tumor risk. Future research in this area should include more detailed coverage of genes in the apoptosis/cell cycle control pathways. ..
  48. Li C, Chen K, Liu Z, Wang L, Gershenwald J, Lee J, et al. Polymorphisms of TP53 Arg72Pro, but not p73 G4C14>A4TA4 and p21 Ser31Arg, contribute to risk of cutaneous melanoma. J Invest Dermatol. 2008;128:1585-8 pubmed
  49. Chen Y, Leal A, Patel S, Gorski D. The homeobox gene GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences. J Biol Chem. 2007;282:507-17 pubmed
    ..The homeobox gene GAX inhibits angiogenesis and induces p21(WAF1/CIP1) expression in vascular ECs...
  50. 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...
  51. Hwang C, Lee C, Kwon K. Extracellular signal-regulated kinase 2-dependent phosphorylation induces cytoplasmic localization and degradation of p21Cip1. Mol Cell Biol. 2009;29:3379-89 pubmed publisher
    p21(Cip1) is an inhibitor of cell cycle progression that promotes G(1)-phase arrest by direct binding to cyclin-dependent kinase and proliferating cell nuclear antigen...
  52. . Polymorphisms in the BRCA1 and ABCB1 genes modulate menopausal hormone therapy associated breast cancer risk in postmenopausal women. Breast Cancer Res Treat. 2010;120:727-36 pubmed publisher
    ..two drug and hormone transporter genes (ABCB1/MDR1 and SHBG), four genes involved in cell cycle regulation (BRCA1, P21/CDKN1A, STK15/AURKA and TP53), six cytokine genes (IGFBP3, IL6, TGFB1, TNF, LTA and IGF1), and two cytokine ..
  53. Taghavi N, Biramijamal F, Abbaszadegan M, Khademi H, Sotoudeh M, Khoshbakht S. P21(waf1/cip1) gene polymorphisms and possible interaction with cigarette smoking in esophageal squamous cell carcinoma in northeastern Iran: a preliminary study. Arch Iran Med. 2010;13:235-42 pubmed
    ..However, the genetic predisposing factors to ESCC in this region have not been clearly defined. The P21(waf1/cip1) gene is involved in the arrest of cellular growth, as induced by the p53 tumor suppressor gene...
  54. Xia X, Ma Q, Li X, Ji T, Chen P, Xu H, et al. Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer. BMC Cancer. 2011;11:399 pubmed publisher
    P21(WAF1/Cip1) binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation...
  55. Kanno S, Maeda N, Tomizawa A, Yomogida S, Katoh T, Ishikawa M. Involvement of p21waf1/cip1 expression in the cytotoxicity of the potent histone deacetylase inhibitor spiruchostatin B towards susceptible NALM-6 human B cell leukemia cells. Int J Oncol. 2012;40:1391-6 pubmed publisher
    ..NALM-6 has higher endogenous p21waf1/cip1 mRNA expression than other leukemia cells...
  56. Ma H, Jin G, Hu Z, Zhai X, Chen W, Wang S, et al. Variant genotypes of CDKN1A and CDKN1B are associated with an increased risk of breast cancer in Chinese women. Int J Cancer. 2006;119:2173-8 pubmed
    p21(Cip1) and p27(Kip1) are cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumor suppressors...
  57. Saramaki A, Banwell C, Campbell M, Carlberg C. Regulation of the human p21(waf1/cip1) gene promoter via multiple binding sites for p53 and the vitamin D3 receptor. Nucleic Acids Res. 2006;34:543-54 pubmed
    The main regulator of the human tumor suppresser gene p21(waf1/cip1) is the transcription factor p53, but more recently it has been suggested to be a primary anti-proliferative target for the nuclear receptor VDR in the presence of its ..
  58. Javelaud D, Besancon F. Inactivation of p21WAF1 sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio. J Biol Chem. 2002;277:37949-54 pubmed
    p21(WAF1) appears to be a major determinant of the cell fate in response to anticancer therapy...
  59. Jung P, Menssen A, Mayr D, Hermeking H. AP4 encodes a c-MYC-inducible repressor of p21. Proc Natl Acad Sci U S A. 2008;105:15046-51 pubmed publisher
    ..cycle reentry of anti-estrogen arrested breast cancer cells and mitogen-mediated repression of the CDK inhibitor p21. AP4 directly repressed p21 by occupying four CAGCTG motifs in the p21 promoter via its basic region...
  60. Lin P, Fosmire S, Park S, Park J, Baksh S, Modiano J, et al. Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance. Mol Cancer. 2007;6:16 pubmed
    ..to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of ..
  61. Poole J, Thain A, Perkins N, Roninson I. Induction of transcription by p21Waf1/Cip1/Sdi1: role of NFkappaB and effect of non-steroidal anti-inflammatory drugs. Cell Cycle. 2004;3:931-40 pubmed
    p21(Waf1/Cip1/Sdi1) is the primary mediator of cell cycle arrest in response to different forms of stress and in the programs of senescence and differentiation...
  62. Schreiber M, Muller W, Singh G, Graham F. Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. Oncogene. 1999;18:1663-76 pubmed
    ..Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter...