Cdkn1a

Summary

Gene Symbol: Cdkn1a
Description: cyclin-dependent kinase inhibitor 1A (P21)
Alias: CAP20, CDKI, CIP1, Cdkn1, P21, SDI1, Waf1, mda6, p21Cip1, p21WAF, cyclin-dependent kinase inhibitor 1, CDK-interacting protein 1, melanoma differentiation-associated protein
Species: mouse
Products:     Cdkn1a

Top Publications

  1. Jones J, Cui X, Medina D, Donehower L. Heterozygosity of p21WAF1/CIP1 enhances tumor cell proliferation and cyclin D1-associated kinase activity in a murine mammary cancer model. Cell Growth Differ. 1999;10:213-22 pubmed
    The p21(WAF1/cIP1) cyclin-dependent kinase (cdk) inhibitor is a regulator of the G(1)-S cell cycle checkpoint. Despite the importance of p21 in cell cycle inhibition, its role as a tumor suppressor is uncertain...
  2. Merched A, Chan L. Absence of p21Waf1/Cip1/Sdi1 modulates macrophage differentiation and inflammatory response and protects against atherosclerosis. Circulation. 2004;110:3830-41 pubmed
    ..A major target of p53 is p21, the cyclin-dependent kinase inhibitor that regulates entry into the cell cycle of different types of cells, ..
  3. Morton J, Jamieson N, Karim S, Athineos D, Ridgway R, Nixon C, et al. LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology. 2010;139:586-97, 597.e1-6 pubmed publisher
    ..Mechanistically, this was associated with decreased p53/p21-dependent growth arrest. Haploinsufficiency for p21 (Cdkn1a) also synergizes with KrasG12D to drive PDAC in the mouse...
  4. Matsumoto A, Takeishi S, Kanie T, Susaki E, Onoyama I, Tateishi Y, et al. p57 is required for quiescence and maintenance of adult hematopoietic stem cells. Cell Stem Cell. 2011;9:262-71 pubmed publisher
    ..Members of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21, p27, p57) have been implicated in HSC quiescence, but loss of p21 or p27 in mice affects HSC quiescence or ..
  5. Mauro M, Rego M, Boisvert R, Esashi F, Cavallo F, Jasin M, et al. p21 promotes error-free replication-coupled DNA double-strand break repair. Nucleic Acids Res. 2012;40:8348-60 pubmed
    b>p21 is a well-established regulator of cell cycle progression. The role of p21 in DNA repair, however, remains poorly characterized...
  6. Jurk D, Wang C, Miwa S, Maddick M, Korolchuk V, Tsolou A, et al. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell. 2012;11:996-1004 pubmed publisher
    ..It was fully rescued by loss of p21(CDKN1A) function in late-generation TERC-/-CDKN1A-/- mice, indicating p21 as the necessary signal transducer between DNA ..
  7. Yang J, Zhang W, Jiang W, Sun X, Han Y, Ding M, et al. P21cip-overexpression in the mouse beta cells leads to the improved recovery from streptozotocin-induced diabetes. PLoS ONE. 2009;4:e8344 pubmed publisher
    ..the pancreatic beta cell regeneration, which could specifically inhibit beta cell proliferation by overexpressing p21(cip) in beta cells via regulation of the Tet-on system...
  8. Fasano C, Dimos J, Ivanova N, Lowry N, Lemischka I, Temple S. shRNA knockdown of Bmi-1 reveals a critical role for p21-Rb pathway in NSC self-renewal during development. Cell Stem Cell. 2007;1:87-99 pubmed publisher
    ..and adult NSC proliferation and self-renewal that, unexpectedly, are mediated by a different cell-cycle inhibitor, p21. Gene array analyses revealed developmental differences in Bmi-1-controlled expression of genes in the p21-Rb cell ..
  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 ..

More Information

Publications80

  1. Yao H, Yang S, Edirisinghe I, Rajendrasozhan S, Caito S, Adenuga D, et al. Disruption of p21 attenuates lung inflammation induced by cigarette smoke, LPS, and fMLP in mice. Am J Respir Cell Mol Biol. 2008;39:7-18 pubmed publisher
    The cyclin-dependent kinase inhibitor p21(CIP1/WAF1/SDI1) (p21) is an important inhibitory checkpoint regulator of cell cycle progression in response to oxidative and genotoxic stresses...
  2. Laine H, Sulg M, Kirjavainen A, Pirvola U. Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev Biol. 2010;337:134-46 pubmed publisher
    ..the spatiotemporal pattern of unscheduled cell cycle re-entry of cochlear hair cells from the p19(Ink4d)/p21(Cip1) compound mutant mice...
  3. Liu Y, Yeh N, Zhu X, Leversha M, Cordon Cardo C, Ghossein R, et al. Somatic cell type specific gene transfer reveals a tumor-promoting function for p21(Waf1/Cip1). EMBO J. 2007;26:4683-93 pubmed
    ..the development of growth-factor-induced oligodendroglioma, we identified a critical role for the Cy elements in p21, and we showed that cyclin D1T286A, which accumulates in the nucleus of p21-deficient cells and binds to cdk4, ..
  4. Marques Torrejon M, Porlan E, Banito A, Gómez Ibarlucea E, López Contreras A, Fernandez Capetillo O, et al. Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell. 2013;12:88-100 pubmed publisher
    ..Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control ..
  5. Porlan E, Morante Redolat J, Marqués Torrejón M, Andreu Agullo C, Carneiro C, Gómez Ibarlucea E, et al. Transcriptional repression of Bmp2 by p21(Waf1/Cip1) links quiescence to neural stem cell maintenance. Nat Neurosci. 2013;16:1567-75 pubmed publisher
    ..Subependymal neural stem cells (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit rapid expansion that is followed by their permanent loss later in life...
  6. Passos J, Nelson G, Wang C, Richter T, Simillion C, Proctor C, et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. 2010;6:347 pubmed publisher
    ..The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling ..
  7. Reijns M, Rabe B, Rigby R, Mill P, Astell K, Lettice L, et al. Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development. Cell. 2012;149:1008-22 pubmed publisher
  8. Kirjavainen A, Sulg M, Heyd F, Alitalo K, Yla Herttuala S, Moroy T, et al. Prox1 interacts with Atoh1 and Gfi1, and regulates cellular differentiation in the inner ear sensory epithelia. Dev Biol. 2008;322:33-45 pubmed publisher
    ..The data point to the tight regulation of phenotypic characteristics of hair cells and supporting cells. ..
  9. Insinga A, Cicalese A, Faretta M, Gallo B, Albano L, Ronzoni S, et al. DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions. Proc Natl Acad Sci U S A. 2013;110:3931-6 pubmed publisher
    ..We show that irradiation of hematopoietic and mammary stem cells up-regulates the cell cycle inhibitor p21, a known target of p53, which prevents p53 activation and inhibits p53 basal activity, impeding apoptosis and ..
  10. Olive M, Mellad J, Beltran L, Ma M, Cimato T, Noguchi A, et al. p21Cip1 modulates arterial wound repair through the stromal cell-derived factor-1/CXCR4 axis in mice. J Clin Invest. 2008;118:2050-61 pubmed publisher
    Cyclin-dependent kinase inhibitors, including p21Cip1, are implicated in cell turnover and are active players in cardiovascular wound repair...
  11. Tateishi Y, Matsumoto A, Kanie T, Hara E, Nakayama K, Nakayama K. Development of mice without Cip/Kip CDK inhibitors. Biochem Biophys Res Commun. 2012;427:285-92 pubmed publisher
    ..Cyclin-dependent kinase (CDK) inhibitors (CKIs) of the Cip/Kip family (p21, p27, and p57) are negative regulators of cell cycle progression and are thought to be essential for development...
  12. Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang X, Leferovich J, et al. Lack of p21 expression links cell cycle control and appendage regeneration in mice. Proc Natl Acad Sci U S A. 2010;107:5845-50 pubmed publisher
    ..mapped and reliable quantitative indicator of regeneration in the MRL mouse, we show that the unrelated Cdkn1a(tmi/Tyj)/J p21(-/-) mouse (unlike the B6129SF2/J WT control) closes ear holes similar to MRL mice, providing a ..
  13. Yao H, Chung S, Hwang J, Rajendrasozhan S, Sundar I, Dean D, et al. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 2012;122:2032-45 pubmed publisher
    ..Activation of SIRT1 may be an attractive therapeutic strategy in COPD/emphysema. ..
  14. Foudi A, Hochedlinger K, Van Buren D, Schindler J, Jaenisch R, Carey V, et al. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol. 2009;27:84-90 pubmed publisher
    ..8-1.8% per day). ..
  15. Martinez P, Flores J, Blasco M. 53BP1 deficiency combined with telomere dysfunction activates ATR-dependent DNA damage response. J Cell Biol. 2012;197:283-300 pubmed publisher
    ..In intact mice, combined 53BP1/TRF1 deficiency in stratified epithelia resulted in earlier onset of DNA damage and increased CHK1 phosphorylation during embryonic development, leading to aggravation of skin phenotypes. ..
  16. Amador V, Ge S, Santamaria P, Guardavaccaro D, Pagano M. APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell. 2007;27:462-73 pubmed
    During the G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored...
  17. Thanasoula M, Escandell J, Martinez P, Badie S, Muñoz P, Blasco M, et al. p53 prevents entry into mitosis with uncapped telomeres. Curr Biol. 2010;20:521-6 pubmed publisher
    ..Here, we report that telomere capping is monitored at the G2/M transition by the p53/p21 damage response pathway...
  18. Pechnick R, Zonis S, Wawrowsky K, Pourmorady J, Chesnokova V. p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Proc Natl Acad Sci U S A. 2008;105:1358-63 pubmed publisher
    ..Cyclin-dependent kinases (CDKs) have a primary role in controlling cell division and cellular proliferation. p21(Cip1) (p21) is a CDK inhibitor that restrains cell cycle progression...
  19. Fujiwara K, Daido S, Yamamoto A, Kobayashi R, Yokoyama T, Aoki H, et al. Pivotal role of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in apoptosis and autophagy. J Biol Chem. 2008;283:388-97 pubmed
    ..The purpose of this study was to show whether the presence of the cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1), a modulator of apoptosis, determines which type of PCD the cell undergoes...
  20. Adeyemi R, Pintel D. Replication of minute virus of mice in murine cells is facilitated by virally induced depletion of p21. J Virol. 2012;86:8328-32 pubmed publisher
    The DNA damage response to infection with minute virus of mice (MVM) leads to activated p53; however, p21 levels are reduced via a proteasome-mediated mechanism...
  21. Kanatsu Shinohara M, Takashima S, Shinohara T. Transmission distortion by loss of p21 or p27 cyclin-dependent kinase inhibitors following competitive spermatogonial transplantation. Proc Natl Acad Sci U S A. 2010;107:6210-5 pubmed publisher
    ..Here we developed a novel transplantation assay for SSCs and demonstrate that p21 and p27 cyclin-dependent kinase inhibitors play critical roles in SSC self-renewal and differentiation...
  22. Valente L, Gray D, Michalak E, Piñón Hofbauer J, Egle A, Scott C, et al. p53 efficiently suppresses tumor development in the complete absence of its cell-cycle inhibitory and proapoptotic effectors p21, Puma, and Noxa. Cell Rep. 2013;3:1339-45 pubmed publisher
    ..which p53 suppresses tumor development, although G1/S boundary cell-cycle arrest via induction of the CDK inhibitor p21 has also been thought to contribute...
  23. Lim S, Chen X, Lim Y, Hanson D, Vo T, Howerton K, et al. Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell. 2008;29:9-22 pubmed publisher
    ..Here we show that, during mouse development, FAK inactivation results in p53- and p21-dependent mesodermal cell growth arrest...
  24. Cozar Castellano I, Haught M, Stewart A. The cell cycle inhibitory protein p21cip is not essential for maintaining beta-cell cycle arrest or beta-cell function in vivo. Diabetes. 2006;55:3271-8 pubmed
    p21(cip1), a regulatory molecule upstream of the G(1/0) checkpoint, is increased in beta-cells in response to mitogenic stimulation...
  25. Lin T, Chao C, Saito S, Mazur S, Murphy M, Appella E, et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol. 2005;7:165-71 pubmed
    ..These findings indicate an alternative mechanism for p53 to maintain genetic stability in ESCs, by inducing the differentiation of ESCs into other cell types that undergo efficient p53-dependent cell-cycle arrest and apoptosis. ..
  26. Zhang P, Wong C, DePinho R, Harper J, Elledge S. Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development. Genes Dev. 1998;12:3162-7 pubmed
    ..These studies demonstrate that p27(KIP1) and p57(KIP2) are critical terminal effectors of signal transduction pathways that control cell differentiation. ..
  27. Prince S, Carreira S, Vance K, Abrahams A, Goding C. Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor. Cancer Res. 2004;64:1669-74 pubmed
    ..The p21(WAF1) cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage...
  28. Nguyen L, Besson A, Heng J, Schuurmans C, Teboul L, Parras C, et al. p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev. 2006;20:1511-24 pubmed
    ..Thus, p27(Kip1) plays a key role in cortical development, acting as a modular protein that independently regulates and couples multiple cellular pathways contributing to neurogenesis. ..
  29. Georgia S, Soliz R, Li M, Zhang P, Bhushan A. p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors. Dev Biol. 2006;298:22-31 pubmed
  30. Cheng T, Rodrigues N, Shen H, Yang Y, Dombkowski D, Sykes M, et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science. 2000;287:1804-8 pubmed
    ..assessed using mice engineered to be deficient in the G1 checkpoint regulator, cyclin-dependent kinase inhibitor, p21cip1/waf1 (p21)...
  31. de la Cueva E, Garcia Cao I, Herranz M, Lopez P, Garcia Palencia P, Flores J, et al. Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma. Oncogene. 2006;25:4128-32 pubmed
    The cell cycle inhibitor p21Waf1/Cip1 is among the most important mediators of the tumor suppressor p53. However, there is increasing evidence indicating that p21 could favor tumorigenesis in specific cell types...
  32. Wang Y, Cui F, Lv Y, Li C, Xu X, Deng C, et al. HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice. Hepatology. 2004;39:318-24 pubmed
    ..HBsAg and HBx genes were integrated into the mouse p21 locus...
  33. Harrelson Z, Kelly R, Goldin S, Gibson Brown J, Bollag R, Silver L, et al. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development. 2004;131:5041-52 pubmed
    ..Despite evidence that TBX2 negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in cultured cells, there is no evidence that loss of Tbx2 function during mouse development results in increased ..
  34. O Reilly M, Staversky R, Watkins R, Reed C, de Mesy Jensen K, Finkelstein J, et al. The cyclin-dependent kinase inhibitor p21 protects the lung from oxidative stress. Am J Respir Cell Mol Biol. 2001;24:703-10 pubmed
    ..induces the tumor suppressor p53 and its downstream target, the cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1) (p21), their role in pulmonary injury remains unknown...
  35. Topley G, Okuyama R, Gonzales J, Conti C, Dotto G. p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a determinant of keratinocyte stem-cell potential. Proc Natl Acad Sci U S A. 1999;96:9089-94 pubmed
    p21(WAF1/Cip1) is one of the best characterized downstream targets of p53, and the growth suppressing function of this cyclin-dependent kinase inhibitor is well established...
  36. Hawke T, Meeson A, Jiang N, Graham S, Hutcheson K, DiMaio J, et al. p21 is essential for normal myogenic progenitor cell function in regenerating skeletal muscle. Am J Physiol Cell Physiol. 2003;285:C1019-27 pubmed
    ..Although mice lacking the cyclin-dependent kinase inhibitor p21 (p21-/-), develop normally, we report here that p21-/- MPCs display increased cell number and enhanced cell cycle ..
  37. Nakayama K. Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development. Bioessays. 1998;20:1020-9 pubmed
    ..In this review, the biological roles of Cip/Kip CKIs in development and tumor suppression are discussed. ..
  38. Zhang X, Li J, Sejas D, Pang Q. The ATM/p53/p21 pathway influences cell fate decision between apoptosis and senescence in reoxygenated hematopoietic progenitor cells. J Biol Chem. 2005;280:19635-40 pubmed
    ..Reoxygenated bone marrow progenitor cells expressed SA-beta-gal and senescence-associated proteins p53 and p21(WAF1)...
  39. Kippin T, Martens D, van der Kooy D. p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev. 2005;19:756-67 pubmed
    Adult stem cells in various tissues are relatively quiescent. The cell cycle inhibitor p21cip1/waf1 (p21) has been shown to be important for maintaining hematopoietic stem cell quiescence and self-renewal...
  40. Condorelli G, Aycock J, Frati G, Napoli C. Mutated p21/WAF/CIP transgene overexpression reduces smooth muscle cell proliferation, macrophage deposition, oxidation-sensitive mechanisms, and restenosis in hypercholesterolemic apolipoprotein E knockout mice. FASEB J. 2001;15:2162-70 pubmed
    ..Ad-mutated(m)-p21WAF/CIP1 transgene overexpression induces a significant reduction of restenosis in hypercholesterolemic apolipoprotein ..
  41. Zhang P, Liegeois N, Wong C, Finegold M, Hou H, Thompson J, et al. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature. 1997;387:151-8 pubmed
  42. Stepniak E, Ricci R, Eferl R, Sumara G, Sumara I, Rath M, et al. c-Jun/AP-1 controls liver regeneration by repressing p53/p21 and p38 MAPK activity. Genes Dev. 2006;20:2306-14 pubmed
    ..This phenotype correlates with increased protein levels of the cdk-inhibitor p21 in the liver...
  43. Bouwman P, Gollner H, Elsasser H, Eckhoff G, Karis A, Grosveld F, et al. Transcription factor Sp3 is essential for post-natal survival and late tooth development. EMBO J. 2000;19:655-61 pubmed
    ..Comparison of the Sp1 and Sp3 knockout phenotype shows that Sp1 and Sp3 have distinct functions in vivo, but also suggests a degree of functional redundancy...
  44. 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...
  45. Cheng M, Olivier P, Diehl J, Fero M, Roussel M, Roberts J, et al. The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 1999;18:1571-83 pubmed
    ..that normal up-regulation of cyclin D- CDK4 in mitogen-stimulated fibroblasts depends redundantly upon p21(Cip1) and p27(Kip1)...
  46. Adhikary S, Peukert K, Karsunky H, Beuger V, Lutz W, Elsässer H, et al. Miz1 is required for early embryonic development during gastrulation. Mol Cell Biol. 2003;23:7648-57 pubmed
    ..Expression of p21Cip1, a target gene of Miz1 is unaltered; in contrast, expression of p57Kip2, another target gene of Miz1 is absent in ..
  47. Jernvall J, Aberg T, Kettunen P, Keranen S, Thesleff I. The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot. Development. 1998;125:161-9 pubmed
    ..in the enamel knot in mouse molar teeth is linked with the expression of the cyclin-dependent kinase inhibitor p21. We show that p21 expression is induced by bone morphogenetic protein 4 (BMP-4) in isolated dental epithelia...
  48. Skapek S, Rhee J, Kim P, Novitch B, Lassar A. Cyclin-mediated inhibition of muscle gene expression via a mechanism that is independent of pRB hyperphosphorylation. Mol Cell Biol. 1996;16:7043-53 pubmed
  49. Aikawa T, Segre G, Lee K. Fibroblast growth factor inhibits chondrocytic growth through induction of p21 and subsequent inactivation of cyclin E-Cdk2. J Biol Chem. 2001;276:29347-52 pubmed
    ..FGF2 increased p21 expression in RCS cells, which assembled with the cyclin E-Cdk2 complexes, although the expression of neither ..
  50. Santiago Raber M, Lawson B, Dummer W, Barnhouse M, Koundouris S, Wilson C, et al. Role of cyclin kinase inhibitor p21 in systemic autoimmunity. J Immunol. 2001;167:4067-74 pubmed
    The cyclin kinase inhibitor protein p21 affects multiple processes relevant to the immune system, including cell cycle progression, replicative senescence, hemopoietic stem cell quiescence, and apoptosis...
  51. Nakajima M, Negishi Y, Tanaka H, Kawashima K. p21(Cip-1/SDI-1/WAF-1) expression via the mitogen-activated protein kinase signaling pathway in insulin-induced chondrogenic differentiation of ATDC5 cells. Biochem Biophys Res Commun. 2004;320:1069-75 pubmed
    ..We have previously clarified that the induction of the cyclin-dependent kinase inhibitor, p21(Cip-1/SDI-1/WAF-1), is essential for chondrogenic differentiation of ATDC5 cells...
  52. Zhang P, Wong C, Liu D, Finegold M, Harper J, Elledge S. p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step. Genes Dev. 1999;13:213-24 pubmed
    ..Here we show that two Cdk inhibitors, p21(CIP1) and p57(KIP2), redundantly control differentiation of skeletal muscle and alveoli in the lungs...
  53. Matsuoka S, Edwards M, Bai C, Parker S, Zhang P, Baldini A, et al. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev. 1995;9:650-62 pubmed
    ..We describe a new CKI, p57KIP2, which is related to p21CIP1 and p27KIP1...
  54. Lin D, Barbash O, Kumar K, Weber J, Harper J, Klein Szanto A, et al. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell. 2006;24:355-66 pubmed
    ..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1. ..
  55. Panic L, Tamarut S, Sticker Jantscheff M, Barkic M, Solter D, Uzelac M, et al. Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation. Mol Cell Biol. 2006;26:8880-91 pubmed
    ..Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program. ..
  56. Salvador J, Hollander M, Nguyen A, Kopp J, Barisoni L, Moore J, et al. Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity. 2002;16:499-508 pubmed
    This study addresses the biological function of the p53-effector genes Gadd45a and p21 in the immune system...
  57. van Os R, Kamminga L, Ausema A, Bystrykh L, Draijer D, van Pelt K, et al. A Limited role for p21Cip1/Waf1 in maintaining normal hematopoietic stem cell functioning. Stem Cells. 2007;25:836-43 pubmed
    Several studies have suggested that the cyclin-dependent kinase (CDK) inhibitor p21 plays a crucial role in regulating hematopoietic stem and progenitor pool size...
  58. Choudhury A, Ju Z, Djojosubroto M, Schienke A, Lechel A, Schaetzlein S, et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet. 2007;39:99-105 pubmed
    ..cells by activation of DNA damage pathways, including upregulation of the cell cycle inhibitor p21 (encoded by Cdkn1a, also known as Cip1 and Waf1)) (refs. 1-5)...
  59. Laine H, Doetzlhofer A, Mantela J, Ylikoski J, Laiho M, Roussel M, et al. p19(Ink4d) and p21(Cip1) collaborate to maintain the postmitotic state of auditory hair cells, their codeletion leading to DNA damage and p53-mediated apoptosis. J Neurosci. 2007;27:1434-44 pubmed
    ..Here we show the synergistic action of another CKI, p21(Cip1), on cell cycle reactivation...
  60. Macleod K, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, et al. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev. 1995;9:935-44 pubmed
    Expression of p21 has been shown to be up-regulated by the p53 tumor suppressor gene in vitro in response to DNA-damaging agents...
  61. Avkin S, Sevilya Z, Toube L, Geacintov N, Chaney S, Oren M, et al. p53 and p21 regulate error-prone DNA repair to yield a lower mutation load. Mol Cell. 2006;22:407-13 pubmed
    ..We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency...
  62. 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,..
  63. Woo M, Hakem R, Furlonger C, Hakem A, Duncan G, Sasaki T, et al. Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol. 2003;4:1016-22 pubmed
    ..b>Cdkn1a encodes p21 (also called Waf1 or Cip1), a cyclin-dependent kinase (CDK) inhibitor...
  64. 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...
  65. Jackson R, Engelman R, Coppola D, Cantor A, Wharton W, Pledger W. p21Cip1 nullizygosity increases tumor metastasis in irradiated mice. Cancer Res. 2003;63:3021-5 pubmed
    p21(Cip1) is a cyclin-dependent kinase inhibitor whose abundance increases in cells exposed to radiation or other DNA-damaging agents. Such increases activate a G1 checkpoint, which allows time for DNA repair before S phase entry...
  66. Brugarolas J, Chandrasekaran C, Gordon J, Beach D, Jacks T, Hannon G. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 1995;377:552-7 pubmed
    The protein p21 is a dual inhibitor of cyclin-dependent kinases and proliferating-cell nuclear antigen (PCNA), both of which are required for passage through the cell cycle. The p21 gene is under the transcriptional control of p53 (ref...
  67. Wu H, Wade M, Krall L, Grisham J, Xiong Y, Van Dyke T. Targeted in vivo expression of the cyclin-dependent kinase inhibitor p21 halts hepatocyte cell-cycle progression, postnatal liver development and regeneration. Genes Dev. 1996;10:245-60 pubmed
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