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. 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)...
  3. 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)...
  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. 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 ..
  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 oncogene,..
  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

Publications93

  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. 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)...
  3. 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)...
  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. 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 ..
  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 oncogene,..
  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. 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...
  16. 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 ..
  17. 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. ..
  18. 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...
  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. Wu G, Fan R, Li W, Ko T, Brattain M. Modulation of cell cycle control by vitamin D3 and its analogue, EB1089, in human breast cancer cells. Oncogene. 1997;15:1555-63 pubmed
    ..in MCF-7 E cells showed that after EB1089 treatment, there was a concentration and time dependent up-regulation of p21 as well as a decrease in cyclin A proteins...
  23. Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T. CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J Biol Chem. 2008;283:29045-52 pubmed publisher
    ..The CDK inhibitor p21, another PCNA-binding protein, is also degraded both in S phase and after UV irradiation...
  24. Zhu H, Nie L, Maki C. Cdk2-dependent Inhibition of p21 stability via a C-terminal cyclin-binding motif. J Biol Chem. 2005;280:29282-8 pubmed
    b>p21 is a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors that includes p21, p27, and p57...
  25. Gong J, Ammanamanchi S, Ko T, Brattain M. Transforming growth factor beta 1 increases the stability of p21/WAF1/CIP1 protein and inhibits CDK2 kinase activity in human colon carcinoma FET cells. Cancer Res. 2003;63:3340-6 pubmed
    ..and cyclin-dependent kinase (CDK) activity after release from growth arrest in association with induction of the p21 CDK inhibitor, whereas cyclins, CDKs, and p27 protein levels remained relatively unchanged...
  26. Fritah A, Saucier C, Mester J, Redeuilh G, Sabbah M. p21WAF1/CIP1 selectively controls the transcriptional activity of estrogen receptor alpha. Mol Cell Biol. 2005;25:2419-30 pubmed
    ..We report here that p21WAF1/CIP1, a cyclin-dependent kinase (Cdk) inhibitor, cooperates with CBP to regulate the ERalpha-mediated transcription of ..
  27. Perucca P, Cazzalini O, Mortusewicz O, Necchi D, Savio M, Nardo T, et al. Spatiotemporal dynamics of p21CDKN1A protein recruitment to DNA-damage sites and interaction with proliferating cell nuclear antigen. J Cell Sci. 2006;119:1517-27 pubmed
    ..Here, we provide evidence that a pool of p21 protein is rapidly recruited to UV-induced DNA-damage sites, where it colocalises with PCNA and PCNA-interacting ..
  28. Koutsodontis G, Moustakas A, Kardassis D. The role of Sp1 family members, the proximal GC-rich motifs, and the upstream enhancer region in the regulation of the human cell cycle inhibitor p21WAF-1/Cip1 gene promoter. Biochemistry. 2002;41:12771-84 pubmed
    ..all six GC-rich motifs (elements 1-6) present in the proximal promoter of the human cell cycle inhibitor p21(WAF-1/Cip1) gene...
  29. Ivanovska I, Ball A, Diaz R, Magnus J, Kibukawa M, Schelter J, et al. MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol. 2008;28:2167-74 pubmed publisher
    ..Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A...
  30. Brenner C, Deplus R, Didelot C, Loriot A, Viré E, De Smet C, et al. Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J. 2005;24:336-46 pubmed
    ..In cells with reduced Dnmt3a levels, we observe specific reactivation of the Myc-repressed p21Cip1 gene, whereas the expression of Myc-activated E-boxes genes is unchanged...
  31. Frouin I, Maga G, Denegri M, Riva F, Savio M, Spadari S, et al. Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partners. J Biol Chem. 2003;278:39265-8 pubmed
    ..Unexpectedly, PARP-1 activity also decreased in the presence of p21waf1/cip1. By pull-down experiments, we provided the first evidence for an association between PARP-1 and p21, which involves ..
  32. Zhang Y, Wang Z, Magnuson N. Pim-1 kinase-dependent phosphorylation of p21Cip1/WAF1 regulates its stability and cellular localization in H1299 cells. Mol Cancer Res. 2007;5:909-22 pubmed
    Previous studies from our laboratory showed that p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle...
  33. Zhu H, Chang B, Uchiumi T, Roninson I. Identification of promoter elements responsible for transcriptional inhibition of polo-like kinase 1 and topoisomerase IIalpha genes by p21(WAF1/CIP1/SDI1). Cell Cycle. 2002;1:59-66 pubmed
    Induction of p21 (WAF1/CIP1/SDI1), a physiological mediator of cell cycle arrest, inhibits multiple genes involved in cell division...
  34. Lee J, Lee S, Namkoong S, Um S, Sull J, Jee S, et al. Gene-gene and gene-environmental interactions of p53, p21, and IRF-1 polymorphisms in Korean women with cervix cancer. Int J Gynecol Cancer. 2004;14:118-25 pubmed
    ..The single nucleotide polymorphisms (SNPs) of p53 codon 72, p21 codon 31, and interferon regulatory factor-1 (IRF-1) intron 6 were evaluated from extracted DNA of peripheral blood ..
  35. Chen W, Sun Z, Wang X, Jiang T, Huang Z, Fang D, et al. Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell. 2009;34:663-73 pubmed publisher
    In response to oxidative stress, Nrf2 and p21(Cip1/WAF1) are both upregulated to protect cells from oxidative damage...
  36. Wu X, Gao H, Ke W, Hager M, Xiao S, Freeman M, et al. VentX trans-activates p53 and p16ink4a to regulate cellular senescence. J Biol Chem. 2011;286:12693-701 pubmed publisher
    ..Here, we show that VentX is a direct transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways...
  37. Howell M, Fairchild H, Kim B, Bin L, Boguniewicz M, Redzic J, et al. Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation. J Invest Dermatol. 2008;128:2248-58 pubmed publisher
    ..Interference of S100/A11 expression, by siRNA, inhibited induction of HBD-3 and FLG. Furthermore p21, a cyclin-dependent kinase inhibitor downstream of S100/A11, was required for calcium-mediated induction of HBD-3 ..
  38. Tian Q, Lu W, Chen H, Ye F, Xie X. The nonsynonymous single-nucleotide polymorphisms in codon 31 of p21 gene and the susceptibility to cervical cancer in Chinese women. Int J Gynecol Cancer. 2009;19:1011-4 pubmed publisher
    It was suggested that single-nucleotide polymorphisms in p21 codon 31 seem to be associated with a variety of human malignancies; very few studies have focused on the association between p21 codon 31 polymorphisms and cervical cancer...
  39. Polakova V, Pardini B, Naccarati A, Landi S, Slyskova J, Novotny J, et al. Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Hum Mutat. 2009;30:661-8 pubmed publisher
    ..006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. ..
  40. Lin J, Reichner C, Wu X, Levine A. Analysis of wild-type and mutant p21WAF-1 gene activities. Mol Cell Biol. 1996;16:1786-93 pubmed
    ..The p21WAF-1 binding sites for cyclins (residues 21 to 26), cdk2 (residues 49 to 71), and proliferating-cell nuclear antigen (residues 124 to 164) have all been mapped to discrete sites on the protein. ..
  41. 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) ..
  42. 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...
  43. 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...
  44. 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...
  45. 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...
  46. 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...
  47. 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...
  48. 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 ..
  49. 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-..
  50. 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-..
  51. 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)...
  52. 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 ..
  53. 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. ..
  54. 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...
  55. 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 ..
  56. 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 ..
  57. 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...
  58. 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...
  59. 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...
  60. 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...
  61. 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...
  62. 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...
  63. 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)...
  64. 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...
  65. 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. ..
  66. 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...
  67. 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...
  68. 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
  69. 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...
  70. 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 ..
  71. 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...
  72. 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...
  73. 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...
  74. 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...
  75. 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...
  76. . 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 ..
  77. 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...
  78. 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...
  79. 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 ..
  80. 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...
  81. 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...