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
    ..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

Publications112 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 oncogene,..
  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. Harper J, Adami G, Wei N, Keyomarsi K, Elledge S. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75:805-16 pubmed
    ..CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-..
  16. Oh H, Mammucari C, Nenci A, Cabodi S, Cohen S, Dotto G. Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1). Proc Natl Acad Sci U S A. 2002;99:5430-5 pubmed
    ..We report here that the TSG101 protein binds to the cyclin/cyclin-dependent kinase (CDK) inhibitor (CKI) p21(Cip1/WAF1) and increases stability of the p21 protein in HEK293F cells and differentiating primary keratinocytes, ..
  17. Dupont J, Karas M, LeRoith D. The cyclin-dependent kinase inhibitor p21CIP/WAF is a positive regulator of insulin-like growth factor I-induced cell proliferation in MCF-7 human breast cancer cells. J Biol Chem. 2003;278:37256-64 pubmed
    ..MCF-7 cells transiently overexpressing p21 showed increased basal and IGF-I-induced thymidine incorporation...
  18. Behnsawy H, Miyake H, Abdalla M, Sayed M, Ahmed A, Fujisawa M. Expression of cell cycle-associated proteins in non-muscle-invasive bladder cancer: correlation with intravesical recurrence following transurethral resection. Urol Oncol. 2011;29:495-501 pubmed publisher
    ..Expression levels of 7 cell cycle-associated proteins, including Aurora-A, c-erbB2, cyclin-D1, Ki-67, p21, p27, and p53, in TUR specimens were measured by immunohistochemical staining...
  19. El Deiry W, Tokino T, Velculescu V, Levy D, Parsons R, Trent J, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817-25 pubmed
    ..Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line...
  20. Duan Z, Zarebski A, Montoya Durango D, Grimes H, Horwitz M. Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Mol Cell Biol. 2005;25:10338-51 pubmed
    ..Gfi1 associates with G9a and HDAC1 on the promoter of the cell cycle regulator p21Cip/WAF1, resulting in an increase in K9 dimethylation at histone H3...
  21. Soria G, Speroni J, Podhajcer O, Prives C, Gottifredi V. p21 differentially regulates DNA replication and DNA-repair-associated processes after UV irradiation. J Cell Sci. 2008;121:3271-82 pubmed publisher
    Although p21 upregulation is required to block cell-cycle progression following many types of genotoxic insult, UV irradiation triggers p21 proteolysis...
  22. Mottet D, Pirotte S, Lamour V, Hagedorn M, Javerzat S, Bikfalvi A, et al. HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism. Oncogene. 2009;28:243-56 pubmed publisher
    ..effective against cancer in clinical trials, at least in part, through transcriptional reactivation of the p21(WAF1/Cip1)gene. The HDACs that regulate p21(WAF1/Cip1) are not fully identified...
  23. Sekiguchi T, Hunter T. Induction of growth arrest and cell death by overexpression of the cyclin-Cdk inhibitor p21 in hamster BHK21 cells. Oncogene. 1998;16:369-80 pubmed
    b>p21cip1/waf1/sdi1 is a universal cyclin-Cdk kinase inhibitor that has two functional domains; one binds and inhibits cyclin-Cdk activity and the other binds PCNA and thereby inhibits elongation by DNA polymerase...
  24. Choi H, Tucker S, Huang Z, Gillenwater A, Luna M, Batsakis J, et al. Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis. Int J Oncol. 2003;22:409-14 pubmed
    The cyclin-dependent kinase inhibitors p27Kip1 and p21WAF1/Cip1 play important roles in cell-cycle regulation...
  25. Whitson J, Noonan E, Pookot D, Place R, Dahiya R. Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma. Int J Cancer. 2009;125:446-52 pubmed publisher
    ..Here, we report further evidence on the potential of dsRNA mediated p21 induction...
  26. Wu S, Huang S, Ding J, Zhao Y, Liang L, Liu T, et al. Multiple microRNAs modulate p21Cip1/Waf1 expression by directly targeting its 3' untranslated region. Oncogene. 2010;29:2302-8 pubmed publisher
    Cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21Cip1/Waf1, is a master downstream effector of tumor suppressors...
  27. Li Y, Dowbenko D, Lasky L. AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival. J Biol Chem. 2002;277:11352-61 pubmed
    p21(Cip1/WAF1) (p21), a p53-inducible protein, is a critical regulator of cell cycle and cell survival. p21 binds to and inhibits both the DNA synthesis regulator proliferating cell nuclear antigen and cyclin A/E-CDK2 complexes...
  28. Seoane J, Le H, Shen L, Anderson S, Massague J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell. 2004;117:211-23 pubmed
    ..Smad proteins activated by TGF-beta form a complex with FoxO proteins to turn on the growth inhibitory gene p21Cip1. This process is negatively controlled by the PI3K pathway, a known inhibitor of FoxO localization in the nucleus,..
  29. Lacy E, Wang Y, Post J, Nourse A, Webb W, Mapelli M, et al. Molecular basis for the specificity of p27 toward cyclin-dependent kinases that regulate cell division. J Mol Biol. 2005;349:764-73 pubmed
    ..the MRAIL sequence in one helix that, in the cell cycle cyclins, mediates specific interactions with domain 1 of p21 and p27...
  30. Fenouille N, Robert G, Tichet M, Puissant A, Dufies M, Rocchi S, et al. The p53/p21Cip1/?Waf1 pathway mediates the effects of SPARC on melanoma cell cycle progression. Pigment Cell Melanoma Res. 2011;24:219-32 pubmed publisher
    ..of SPARC induces G2/M cell cycle arrest and tumor growth inhibition with activation of p53 and induction of p21(Cip1/Waf1) acting as a checkpoint, preventing efficient mitotic progression...
  31. 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...
  32. 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...
  33. 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...
  34. Yang W, Qi Q, Zhang H, Xu W, Chen Z, Wang L, et al. p21 Waf1/Cip1 polymorphisms and risk of esophageal cancer. Ann Surg Oncol. 2010;17:1453-8 pubmed publisher
    As the main downstream effecter of tumor suppressor p53, p21(Waf1/Cip1) functions as a unique link from p53 to cell-cycle arrest and DNA repair. In contrast to p53, p21(Waf1/Cip1) has general rare mutations...
  35. 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...
  36. Huang S, Wu W, Chang W, Wu M, Chen Y, Chen Y, et al. p53 Codon 72 and p21 codon 31 polymorphisms in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2004;13:2217-24 pubmed
    The tumor suppressor gene p53 and its downstream effector p21 are thought to play major roles in the development of human malignancy...
  37. 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 ..
  38. Liu F, Li B, Wei Y, Chen X, Ma Y, Yan L, et al. P21 codon 31 polymorphism associated with cancer among white people: evidence from a meta-analysis involving 78,074 subjects. Mutagenesis. 2011;26:513-21 pubmed publisher
    b>p21 protein is a cell cycle regulator that induces G1 arrest, leading to DNA repair or apoptosis. Previous studies have shown that p21 polymorphism in codon 31 (Ser 31 Arg) may play a role in susceptibility to cancer...
  39. 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 ..
  40. Qiu L, Zhang J, Zhu X, Zheng C, Sun S, Wang Z, et al. The p21 Ser31Arg polymorphism and breast cancer risk: a meta-analysis involving 51,236 subjects. Breast Cancer Res Treat. 2010;124:475-9 pubmed publisher
    Published data on the association between p21 Ser31Arg polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed...
  41. Zhao Y, Wang C, Wu Y, Ma S, Ji Y, Lu Y. P21 (waf1/cip1) is required for non-small cell lung cancer sensitive to Gefitinib treatment. Biomed Pharmacother. 2011;65:151-6 pubmed publisher
    ..Here, we show that Gefitinib reduces p-Akt levels, concomitant with elevation of p21 levels and suppression of cdk2/4 and cyclinE/D1 activities which result in impaired cell cycle progression through ..
  42. 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...
  43. 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 ..
  44. 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...
  45. 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...
  46. Scott M, Morrice N, Ball K. Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding. J Biol Chem. 2000;275:11529-37 pubmed
    The p53-inducible gene product p21(WAF1/CIP1) plays a critical role in regulating the rate of tumor incidence, and identifying mechanisms of its post-translational regulation will define key pathways that link growth control to p21-..
  47. 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...
  48. 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 ..
  49. Xi Y, Ding K, Su X, Chen D, You W, Shen Y, et al. p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions. Carcinogenesis. 2004;25:2201-6 pubmed
    ..In this study we investigated correlations of the p53 variations at codon 72 and p21(WAF1/CIP1) haplotype with the risk of intestinal gastric carcinoma...
  50. Kao J, Chuah S, Huang C, Chen C, Wang C, Hung C, et al. P21/WAF1 is an independent survival prognostic factor for patients with hepatocellular carcinoma after resection. Liver Int. 2007;27:772-81 pubmed
    The cyclin kinase inhibitor p21/WAF1 is regulated by p53-dependent or independent pathways and inhibits the action of proliferating cell nuclear antigen (PCNA)...
  51. 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...
  52. Chen W, Wu H, Hsu C, Chen H, Tsai F. p21 gene codon 31 polymorphism is associated with bladder cancer. Urol Oncol. 2002;7:63-6 pubmed
    The function of p21 is related to cell apoptosis, progression and malignancies. It is thought that p21 is related to cancer formation but is not related to tumor grade...
  53. Li G, Liu Z, Sturgis E, Shi Q, Chamberlain R, Spitz M, et al. Genetic polymorphisms of p21 are associated with risk of squamous cell carcinoma of the head and neck. Carcinogenesis. 2005;26:1596-602 pubmed
    The p21 (Waf1/Cip1/CDKN1A) protein regulates the transition from the G1 to the S phase and has an important role in modulating cell-cycle control, apoptosis and cell growth...
  54. 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 ..
  55. 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...
  56. 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...
  57. 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. ..
  58. 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. ..
  59. 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...
  60. Rodrigues F, Kawasaki Oyama R, Fo J, Ukuyama E, Antonio J, Bozola A, et al. Analysis of CDKN1A polymorphisms: markers of cancer susceptibility?. Cancer Genet Cytogenet. 2003;142:92-8 pubmed
    ..05). The results suggest that this polymorphism affects TP21 transactivator binding and may be important during the pathogenesis of skin cancer. ..
  61. Bau D, Tsai M, Lo Y, Hsu C, Tsai Y, Lee C, et al. Association of p53 and p21(CDKN1A/WAF1/CIP1) polymorphisms with oral cancer in Taiwan patients. Anticancer Res. 2007;27:1559-64 pubmed
    The tumor suppressor gene p53 and its downstream effector p21(CDKN1A/WAF1/CIP1) are thought to play major roles in the development of human malignancy...
  62. 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 ..
  63. 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...
  64. 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)...
  65. 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-..
  66. 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-..
  67. 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...
  68. 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...
  69. 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...
  70. 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...
  71. 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 differential ..
  72. 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...
  73. 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 ..
  74. 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 ..
  75. 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...
  76. 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...
  77. 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 ..
  78. 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. ..
  79. 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...
  80. 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...
  81. 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)...
  82. 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...
  83. 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...
  84. 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...
  85. 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 ..
  86. 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...
  87. 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...
  88. 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...
  89. 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...
  90. 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. ..