Gene Symbol: Cdkn1a
Description: cyclin-dependent kinase inhibitor 1A
Alias: Cip1, UV96, Waf1, cyclin-dependent kinase inhibitor 1, cyclin-dependent kinase inhibitor 1A (P21), cyclin-dependent kinase inhibitor 1A (p21, Cip1)
Species: rat
Products:     Cdkn1a

Top Publications

  1. Zhang C, Kavurma M, Lai A, Khachigian L. Ets-1 protects vascular smooth muscle cells from undergoing apoptosis by activating p21WAF1/Cip1: ETS-1 regulates basal and and inducible p21WAF1/Cip: ETS-1 regulates basal and inducible p21WAF1/Cip1 transcription via distinct cis-acting elements in . J Biol Chem. 2003;278:27903-9 pubmed
    The cyclin-dependent kinase inhibitor (CKI) p21WAF1/Cip1 is regulated at the level of transcription by nuclear factors such as the co-activator p300...
  2. 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
    ..We suggest that in addition to their roles as inhibitors, the p21 family of proteins, originally identified as inhibitors, may also have roles as adaptor proteins that assemble and program kinase complexes for specific functions. ..
  3. Harms C, Albrecht K, Harms U, Seidel K, Hauck L, Baldinger T, et al. Phosphatidylinositol 3-Akt-kinase-dependent phosphorylation of p21(Waf1/Cip1) as a novel mechanism of neuroprotection by glucocorticoids. J Neurosci. 2007;27:4562-71 pubmed
    ..corticosterone protects neurons from apoptosis by a mechanism involving the cyclin-dependent kinase inhibitor p21(Waf1/Cip1)...
  4. Chou W, Guh J, Tsai J, Hwang C, Chen H, Huang J, et al. Arecoline-induced growth arrest and p21WAF1 expression are dependent on p53 in rat hepatocytes. Toxicology. 2008;243:1-10 pubmed
    ..5mM)-inhibited cell proliferation at 24h. Arecoline (0.5mM) also increased p21(WAF1) protein expression and p21(WAF1) gene transcription. Moreover, arecoline (0...
  5. Timchenko N, Harris T, Wilde M, Bilyeu T, Burgess Beusse B, Finegold M, et al. CCAAT/enhancer binding protein alpha regulates p21 protein and hepatocyte proliferation in newborn mice. Mol Cell Biol. 1997;17:7353-61 pubmed
  6. Dong Y, Chi S, Borowsky A, Fan Y, Weiss R. Cytosolic p21Waf1/Cip1 increases cell cycle transit in vascular smooth muscle cells. Cell Signal. 2004;16:263-9 pubmed
    ..While initially described as a cyclin kinase inhibitor, p21Waf1/Cip1 has since been shown to have bimodal effects on cell cycle progression and cell proliferation, and evidence is ..
  7. Tsai F, Lin H, Chen W, Tsai C, Tsai S. A codon 31ser-arg polymorphism of the WAF-1/CIP-1/p21/tumour suppressor gene in Chinese primary open-angle glaucoma. Acta Ophthalmol Scand. 2004;82:76-80 pubmed
    ..389, 95% confidence interval: 1.14-5.01). This study suggests that an association exists between the Arg allele of the p21 codon 31 polymorphism and POAG in the Chinese population. ..
  8. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev. 2008;22:2496-506 pubmed publisher
    ..Finally, we show that the CRL4(Cdt2) and the SCF(Skp2) ubiquitin ligases are redundant with each other in promoting the degradation of p21 during an unperturbed S phase of the cell cycle. ..
  9. Yuen P, Chow V, Choy J, Lam K, Ho W, Wei W. The clinicopathologic significance of p53 and p21 expression in the surgical management of lingual squamous cell carcinoma. Am J Clin Pathol. 2001;116:240-5 pubmed
    ..Overexpression of p21 but not p53 has prognostic value for survival in the surgical treatment of lingual carcinomas. The combination of stage with p21 expression is recommended for evaluation of prognosis and for management planning. ..

More Information

Publications104 found, 100 shown here

  1. McBride S, Leonard N, Reynolds N. Loss of p21(WAF1) compartmentalisation in sebaceous carcinoma compared with sebaceous hyperplasia and sebaceous adenoma. J Clin Pathol. 2002;55:763-6 pubmed
    ..p21(WAF1) is a nuclear protein that regulates cell cycle progression...
  2. Nemes J, Nemes Z, Marton I. p21WAF1/CIP1 expression is a marker of poor prognosis in oral squamous cell carcinoma. J Oral Pathol Med. 2005;34:274-9 pubmed
    Previous research on the prognostic relevance of p21(WAF1/CIP1) in oral squamous cell carcinomas (OSCC) yielded inconclusive and contradictory data...
  3. Kondo M, Tajinda K, Colantuoni C, Hiyama H, Seshadri S, Huang B, et al. Unique pharmacological actions of atypical neuroleptic quetiapine: possible role in cell cycle/fate control. Transl Psychiatry. 2013;3:e243 pubmed publisher
    ..genes were differentially expressed upon exposure to quetiapine compared with haloperidol or vehicle; among them, Cdkn1a, the gene encoding p21, exhibited the greatest fold change relative to haloperidol...
  4. Tong Y, Wang Y, Ding Y, Li J, Pan X, Lu X, et al. Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Facilitates the Development of Cardiac Hypertrophy. Cell Physiol Biochem. 2017;42:1645-1656 pubmed publisher
    ..p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution ..
  5. Connell Crowley L, Harper J, Goodrich D. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell. 1997;8:287-301 pubmed
    ..This study identifies a residue whose phosphorylation is critical for inactivation of pRb-mediated growth suppression, and it indicates that hyperphosphorylation and inactivation of pRb are not necessarily synonymous. ..
  6. Ishido M, Kami K, Masuhara M. In vivo expression patterns of MyoD, p21, and Rb proteins in myonuclei and satellite cells of denervated rat skeletal muscle. Am J Physiol Cell Physiol. 2004;287:C484-93 pubmed
    ..The present study provides a molecular basis to further understand the function of MyoD expressed in the myonuclei and satellite cell nuclei of denervated skeletal muscle. ..
  7. Lees S, Childs T, Booth F. p21(Cip1) expression is increased in ambient oxygen, compared to estimated physiological (5%) levels in rat muscle precursor cell culture. Cell Prolif. 2008;41:193-207 pubmed publisher
    ..we hypothesized that 20% O2 in culture represents a sufficient stimulus to cause increased expression of two key negative regulators of the cell-cycle Cip/Kip family of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1), in MPCs.
  8. Zheng B, Han M, Shu Y, Li Y, Miao S, Zhang X, et al. HDAC2 phosphorylation-dependent Klf5 deacetylation and RAR? acetylation induced by RAR agonist switch the transcription regulatory programs of p21 in VSMCs. Cell Res. 2011;21:1487-508 pubmed publisher
  9. Chen P, Li Y, Toback F. AMP-18 Targets p21 to Maintain Epithelial Homeostasis. PLoS ONE. 2015;10:e0125490 pubmed publisher for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle ..
  10. Lukas J, Groshen S, Saffari B, Niu N, Reles A, Wen W, et al. WAF1/Cip1 gene polymorphism and expression in carcinomas of the breast, ovary, and endometrium. Am J Pathol. 1997;150:167-75 pubmed
    ..b>WAF1/Cip1, also known as WAF1, Cip1, sdi1, or CAP20, codes for a 21-kd protein (p21WAF1/Cip1), which was recently ..
  11. Park J, Schutzer W, Lindsley J, Bagby S, Oyama T, Anderson S, et al. p21 is decreased in polycystic kidney disease and leads to increased epithelial cell cycle progression: roscovitine augments p21 levels. BMC Nephrol. 2007;8:12 pubmed
  12. Wang H, Hsu S, Lee W. Extra-Nuclear Signaling Pathway Involved in Progesterone-Induced Up-Regulations of p21cip1 and p27kip1 in Male Rat Aortic Smooth Muscle Cells. PLoS ONE. 2015;10:e0125903 pubmed publisher
    ..The findings of the present study highlight the molecular mechanism underlying P4-induced up-regulations in p21cip1 and p27kip1 in RASMCs. ..
  13. Diehl J, Yang W, Rimerman R, Xiao H, Emili A. Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase. Mol Cell Biol. 2003;23:1764-74 pubmed
    ..In addition, our data demonstrate that Hsc70 remains bound to cyclin D1 following its assembly with CDK4 and Cip/Kip proteins, where it ensures the formation of a catalytically active complex. ..
  14. Shibue T, Takeda K, Oda E, Tanaka H, Murasawa H, Takaoka A, et al. Integral role of Noxa in p53-mediated apoptotic response. Genes Dev. 2003;17:2233-8 pubmed
    ..genotoxic stresses, under which p53 activates both survival and apoptotic pathways through induction of p21(WAF1/Cip1) and Noxa, respectively...
  15. He Y, Zhang X, Zeng X, Huang Y, Wei J, Han L, et al. HuR-mediated posttranscriptional regulation of p21 is involved in the effect of Glycyrrhiza uralensis licorice aqueous extract on polyamine-depleted intestinal crypt cells proliferation. J Nutr Biochem. 2012;23:1285-93 pubmed publisher
    ..These results demonstrate that licorice can exert its action on stimulating the growth of intestinal crypt cells by regulating p21 mRNA level at the posttranscriptional level by HuR. ..
  16. Braun K, Hölzl G, Soucek T, Geisen C, Moroy T, Hengstschlager M. Investigation of the cell cycle regulation of cdk3-associated kinase activity and the role of cdk3 in proliferation and transformation. Oncogene. 1998;17:2259-69 pubmed
    ..Our data provide first insights into the regulation of cdk3-associated kinase activity and suggest a model how cdk3 participates in the regulation of the G1-S transition. ..
  17. Hirota M, Ito T, Okudela K, Kawabe R, Yazawa T, Hayashi H, et al. Cell proliferation activity and the expression of cell cycle regulatory proteins in oral lichen planus. J Oral Pathol Med. 2002;31:204-12 pubmed
    ..These complex changes, which concomitantly occur in the injured mucosal epithelium, could contribute to the development and maintenance of characteristic mucosal epithelial architectures seen in OLP. ..
  18. Mönkemann H, De Vriese A, Blom H, Kluijtmans L, Heil S, Schild H, et al. Early molecular events in the development of the diabetic cardiomyopathy. Amino Acids. 2002;23:331-6 pubmed
    ..To analyze the mechanism of overexpression of p21(WAF1/CIP1) and inhibition of cyclin D(1) expression in cardiomyocytes of diabetic rats we examined the methylation ..
  19. García Tuñón I, Ricote M, Ruiz A, Fraile B, Paniagua R, Royuela M. Cell cycle control related proteins (p53, p21, and Rb) and transforming growth factor beta (TGFbeta) in benign and carcinomatous (in situ and infiltrating) human breast: implications in malignant transformations. Cancer Invest. 2006;24:119-25 pubmed
    ..In the infiltrating tumors, the expression of p21 in the nuclei and the decrease in pRb expression suggest an insufficient attempt to hinder cell proliferation. ..
  20. Okamoto H, Fujioka Y, Takahashi A, Takahashi T, Taniguchi T, Ishikawa Y, et al. Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1). J Atheroscler Thromb. 2006;13:183-91 pubmed
    ..The p21(WAF1) cyclin-dependent kinase inhibitor regulates cell-cycle progression, senescence, and differentiation in injured ..
  21. Sham C, To K, Chan P, Lee D, Tong M, van Hasselt C. Prevalence of human papillomavirus, Epstein-Barr virus, p21, and p53 expression in sinonasal inverted papilloma, nasal polyp, and hypertrophied turbinate in Hong Kong patients. Head Neck. 2012;34:520-33 pubmed publisher
    ..HPV prevalence of our IP is low. EBV is not present in IP. High p21 and low p53 expression in IP suggests a non-p53-dependent regulation pathway. ..
  22. de Andrade B, Leon J, Carlos R, Delgado Azañero W, Mosqueda Taylor A, de Almeida O. Immunohistochemical expression of p16, p21, p27 and cyclin D1 in oral nevi and melanoma. Head Neck Pathol. 2012;6:297-304 pubmed publisher
    ..The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions. ..
  23. Kwon Y, Jovanovic A, Serfas M, Tyner A. The Cdk inhibitor p21 is required for necrosis, but it inhibits apoptosis following toxin-induced liver injury. J Biol Chem. 2003;278:30348-55 pubmed
    Liver injury and repair were examined in wild type, p21Waf1/Cip1, and p27Kip1-deficient mice following carbon tetrachloride (CCl4) administration...
  24. 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...
  25. Santiago F, Ishii H, Shafi S, Khurana R, Kanellakis P, Bhindi R, et al. Yin Yang-1 inhibits vascular smooth muscle cell growth and intimal thickening by repressing p21WAF1/Cip1 transcription and p21WAF1/Cip1-Cdk4-cyclin D1 assembly. Circ Res. 2007;101:146-55 pubmed
    ..YY1 inhibits p21(WAF1/Cip1) transcription, prevents assembly of a p21(WAF1/Cip1)-cdk4-cyclin D1 complex, and blocks downstream pRb(Ser249/..
  26. Sasaki M, Ikeda H, Nakanuma Y. Activation of ATM signaling pathway is involved in oxidative stress-induced expression of mito-inhibitory p21WAF1/Cip1 in chronic non-suppurative destructive cholangitis in primary biliary cirrhosis: an immunohistochemical study. J Autoimmun. 2008;31:73-8 pubmed publisher
    ..chronic non-suppurative destructive cholangitis (CNSDC) in primary biliary cirrhosis (PBC) reportedly express p21(WAF1/Cip1) and p16(INK4a), which may induce cell cycle arrest and are related to progressive loss of BECs of PBC...
  27. Mallick S, D Mello S. JAZ (Znf346), a SIRT1-interacting protein, protects neurons by stimulating p21 (WAF/CIP1) protein expression. J Biol Chem. 2014;289:35409-20 pubmed publisher
    ..Although not affecting the expression of several cyclins, overexpression of JAZ stimulates expression of p21 (WAF1/CIP1), a cell cycle inhibitor known to have neuroprotective effects...
  28. Ho D, Kim H, Kim J, Sim H, Ahn H, Kim J, et al. Leucine-Rich Repeat Kinase 2 (LRRK2) phosphorylates p53 and induces p21(WAF1/CIP1) expression. Mol Brain. 2015;8:54 pubmed publisher
    ..LRRK2 mediated p53 phosphorylation translocalizes p53 predominantly to nucleus and increases p21(WAF1/CIP1) expression in SH-SY5Y cells based on reverse transcription-polymerase chain reaction and Western blot assay ..
  29. Zu G, Yao J, Ji A, Ning S, Luo F, Li Z, et al. Nurr1 promotes intestinal regeneration after ischemia/reperfusion injury by inhibiting the expression of p21 (Waf1/Cip1). J Mol Med (Berl). 2017;95:83-95 pubmed publisher
    ..Nurr1 knockdown led to G1-phase arrest mediated by p21 (Waf1/Cip1) activation, but Nurr1 overexpression reduced the proportion of IEC-6 cells in G1 phase as a result of p21 ..
  30. Huang Z, Wu Y, Hedrick N, Gutmann D. T-cadherin-mediated cell growth regulation involves G2 phase arrest and requires p21(CIP1/WAF1) expression. Mol Cell Biol. 2003;23:566-78 pubmed
    ..T-cadherin-expressing C6 cell lines exhibited increased p21(CIP1/WAF1), but not p27(Kip1), expression...
  31. Yamashita S, Wakazono K, Nomoto T, Tsujino Y, Kuramoto T, Ushijima T. Expression quantitative trait loci analysis of 13 genes in the rat prostate. Genetics. 2005;171:1231-8 pubmed
    ..Nine genes [Aldh1a1, Aldr1, Bmp6, Cdkn1a (p21), Cntn6, Ghr, Jund, Nupr1, and RT1-M3] were controlled by cis-acting loci...
  32. 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...
  33. 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 ..
  34. Shibata E, Abbas T, Huang X, Wohlschlegel J, Dutta A. Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin-conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex. Mol Cell Biol. 2011;31:3136-45 pubmed publisher
    ..These findings identify the UBCs required for the activity of CRL4(Cdt2) on multiple substrates and demonstrate that different UBCs are involved in the selective ubiquitylation of different substrates by the same E3 complex. ..
  35. Zhang D, Wang H, Tan Y. Wnt/?-catenin signaling induces the aging of mesenchymal stem cells through the DNA damage response and the p53/p21 pathway. PLoS ONE. 2011;6:e21397 pubmed publisher
  36. Xie X, Clausen O, Boysen M. Prognostic significance of p21WAF1/CIP1 expression in tongue squamous cell carcinomas. Arch Otolaryngol Head Neck Surg. 2002;128:897-902 pubmed
    To investigate the prognostic significance of p21(WAF1/CIP1) expression and its relationship with p53 accumulation and other apoptotic markers such as Bax, Bcl-2, and apoptotic index in relation to disease-specific survival in oral tongue ..
  37. Kavurma M, Khachigian L. Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells by repressing p21WAF1/Cip1 transcription and cyclin D1-Cdk4-p21WAF1/Cip1 complex formation. J Biol Chem. 2003;278:32537-43 pubmed
    ..molecular mechanism via its capacity to repress the expression of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 at the level of transcription, mRNA, and protein...
  38. 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...
  39. Vitiello P, Staversky R, Gehen S, Johnston C, Finkelstein J, Wright T, et al. p21Cip1 protection against hyperoxia requires Bcl-XL and is uncoupled from its ability to suppress growth. Am J Pathol. 2006;168:1838-47 pubmed
    The cyclin-dependent kinase inhibitor p21Cip1/Waf1/Sdi1 protects the lung against hyperoxia, but the mechanism of protection remains unclear because loss of p21 does not lead to aberrant cell proliferation...
  40. Kataoka T, Tsukamoto Y, Matsumura M, Miyake A, Kamiura S, Ishiguro S, et al. Expression of p21Cip1/Waf1 and p27Kip1 in small cell neuroendocrine carcinoma of the uterine cervix. Int J Surg Pathol. 2008;16:11-5 pubmed publisher
    ..Immunohistochemical methods were used to compare the expression of p21Cip1/Waf1 and p27Kip1 in SCCC and squamous cell carcinoma, the most common type of cervical cancer...
  41. Raut S, Singh G, Rastogi B, Saikia U, Mittal A, Dogra N, et al. miR-30c and miR-181a synergistically modulate p53-p21 pathway in diabetes induced cardiac hypertrophy. Mol Cell Biochem. 2016;417:191-203 pubmed publisher
    ..Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53-p21 pathway in DbCM. ..
  42. Bansal R, Marin Husstege M, Bryant M, Casaccia Bonnefil P. S-phase entry of oligodendrocyte lineage cells is associated with increased levels of p21Cip1. J Neurosci Res. 2005;80:360-8 pubmed
    ..Therefore, we propose that p21Cip1 is acting as a positive regulator, rather than an inhibitor, of cell cycle entry by favoring the assembly of active cyclin D1/CDK4 complexes. ..
  43. Wang H, He G, Xu G. [Expression and significance of P53 and P21 in nasal NK/T-cell lymphoma]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2010;41:132-6 pubmed
    ..05). The expressions of P53, P21 and Ki67 proteins are closely related with the pathogenesis and progression of NKTL. Combined detection of P53, P21 and Ki67 could be better to judge the biological behavior of NKTL. ..
  44. Adnane J, Jackson R, Nicosia S, Cantor A, Pledger W, Sebti S. Loss of p21WAF1/CIP1 accelerates Ras oncogenesis in a transgenic/knockout mammary cancer model. Oncogene. 2000;19:5338-47 pubmed
    Upregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and subsequent cell growth arrest or senescence is one mechanism by which normal cells are believed to respond to stress induced by the constitutively activated GTPase Ras...
  45. Ilan N, Cheung L, Miller S, Mohsenin A, Tucker A, Madri J. Pecam-1 is a modulator of stat family member phosphorylation and localization: lessons from a transgenic mouse. Dev Biol. 2001;232:219-32 pubmed
    ..We suggest that by serving as a scaffolding, PECAM-1 can bring substrates (STAT5a) and enzymes (a kinase) into close proximity, thereby modulating phosphorylation levels of selected proteins, as previously noted for beta-catenin. ..
  46. Islam M, Mitsuhashi N, Akimoto T, Sakurai H, Hasegawa M, Ishikawa H, et al. Hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro. Oncol Rep. 2001;8:501-7 pubmed
    ..Western blot analysis showed an increase in expression of p53, p21WAF1/CIP1, Hsp70 proteins in both cell lines after heat-shock at 43 degrees C for 30 min...
  47. 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
    ..Furthermore, these findings suggest that targeting of DNA methyltransferases by transcription factors is a wide and general mechanism for the generation of specific DNA methylation patterns within a cell. ..
  48. Matsuu Matsuyama M, Shichijo K, Okaichi K, Nakayama T, Nakashima M, Uemura T, et al. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells. J Radiat Res. 2008;49:341-7 pubmed
    ..Accumulation of p53, p21(WAF1/CIP1) and Bax expression in the jejunum after irradiation were examined by Western blot analyses...
  49. Szentmary N, Stündl A, Szende B, Suveges I. P21, p27, bax, cathepsin and survivin pathways in macular dystrophy corneas. Histol Histopathol. 2010;25:287-90 pubmed publisher
    ..We conclude that the down-regulation of p21, p27 and cathepsin in epithelial cells of macular dystrophy corneas may be related to defense mechanisms against apoptotic cell death. ..
  50. Porter D, Farmaki E, Altilia S, Schools G, West D, Chen M, et al. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc Natl Acad Sci U S A. 2012;109:13799-804 pubmed publisher
    ..This secretory phenotype was found here to be mediated in part by a damage-inducible cell-cycle inhibitor p21 (CDKN1A). We developed small-molecule compounds that inhibit damage-induced transcription downstream of p21...
  51. Fitzner B, Lange A, Muller S, Jaster R. Cdkn1a is a key mediator of rat pancreatic stellate cell senescence. Pancreatology. 2013;13:254-62 pubmed publisher
    ..Here, we have studied if the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (Cdkn1a, p21/Waf1), expression of which is increased in senescent rat PSC, plays a causative role in the senescence ..
  52. Kovacheva E, Hikim A, Shen R, Sinha I, Sinha Hikim I. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology. 2010;151:628-38 pubmed publisher
    ..Testosterone reverses sarcopenia through stimulation of cellular metabolism and survival pathway together with inhibition of death pathway. ..
  53. Zhang M, Du Y, Lu R, Shu Y, Zhao W, Li Z, et al. Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21Cip1/Waf1 Pathway. Oxid Med Cell Longev. 2016;2016:7524308 pubmed
    ..altered autophagy, and increased G1 cell cycle arrest, ROS production, and expression of p53 and p21Cip1/Waf1 compared with BMSCs of the 1st passage...
  54. Lim Y, Kwon J, Kim D, Lee S, Park R, Lee J, et al. Obovatol from Magnolia obovata inhibits vascular smooth muscle cell proliferation and intimal hyperplasia by inducing p21Cip1. Atherosclerosis. 2010;210:372-80 pubmed publisher
    ..These results also show that obovatol may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis. ..
  55. Kawakami T, Saito R, Takahashi K. Overexpression of p2lWaf1/Cip1 immunohistochemical staining in Bowen's disease, but not in disseminated superficial porokeratosis. Br J Dermatol. 1999;141:647-51 pubmed
    ..p21Waf1/Cip1 is thought to mediate the signal of p53 induced by DNA damaging agents to arrest the cell cycle...
  56. Wall S, Zhong Z, DeClerck Y. The cyclin-dependent kinase inhibitors p15INK4B and p21CIP1 are critical regulators of fibrillar collagen-induced tumor cell cycle arrest. J Biol Chem. 2007;282:24471-6 pubmed
    ..we demonstrate that fibrillar collagen can also arrest cells at the G2 phase, which is mediated in part by p21(CIP1)...
  57. Gomes C, Drummond S, Guimarães A, Andrade C, Mesquita R, Gomez R. P21/ WAF1 and cyclin D1 variants and oral squamous cell carcinoma. J Oral Pathol Med. 2008;37:151-6 pubmed publisher
    ..We evaluated a possible association between CCND1 A870G and P21/WAF1 C98A polymorphisms and OSCC, as well as the impact of the genotypes on protein immunoexpression...
  58. Vaish V, Rana C, Piplani H, Vaiphei K, Sanyal S. Sulindac and Celecoxib regulate cell cycle progression by p53/p21 up regulation to induce apoptosis during initial stages of experimental colorectal cancer. Cell Biochem Biophys. 2014;68:301-19 pubmed publisher
    ..We may conclude that Sulindac and Celecoxib could possibly follow p53/p21 mediated regulation of cell proliferation, where down regulation of NF-?B signaling and activation of PPAR? might serve as important additional events in vivo. ..
  59. Hirao A, Kong Y, Matsuoka S, Wakeham A, Ruland J, Yoshida H, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 2000;287:1824-7 pubmed
    ..Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage. ..
  60. Roh J, Kim J, Park N, Song Y, Park I, Park S, et al. p53 and p21 genetic polymorphisms and susceptibility to endometrial cancer. Gynecol Oncol. 2004;93:499-505 pubmed
    ..These data suggest that there is a significant association between the genetic polymorphisms of p53, p21, and specific combinations of the at-risk genotypes of these genes and the risk of developing endometrial cancer in Korean women. ..
  61. McDonnell T, Chari N, Cho Vega J, Troncoso P, Wang X, Bueso Ramos C, et al. Biomarker expression patterns that correlate with high grade features in treatment naive, organ-confined prostate cancer. BMC Med Genomics. 2008;1:1 pubmed publisher
    ..This observation may have broader implications regarding the determination of risk among patients with prostate cancer that is currently considered to be of either good prognosis or unclear prognosis, i.e. Gleason score 7 tumors. ..
  62. Kiyosaki K, Nakada C, Hijiya N, Tsukamoto Y, Matsuura K, Nakatsuka K, et al. Analysis of p53 mutations and the expression of p53 and p21WAF1/CIP1 protein in 15 cases of sebaceous carcinoma of the eyelid. Invest Ophthalmol Vis Sci. 2010;51:7-11 pubmed publisher
    The purpose of this study was to detect mutation of the p53 gene, to assess its relationship with p53 or p21(WAF1/CIP1) expression, and to evaluate the correlation between p53 mutation or p21(WAF1/CIP1) expression and clinicopathologic ..
  63. Heldring N, Joseph B, Hermanson O, Kioussi C. Pitx2 expression promotes p21 expression and cell cycle exit in neural stem cells. CNS Neurol Disord Drug Targets. 2012;11:884-92 pubmed
    ..Pitx2 expression caused a rapid and dramatic (?20-fold) increase in expression of the cell cycle inhibitor p21 (WAF1/Cip1)...
  64. Serrano M, Lin A, McCurrach M, Beach D, Lowe S. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593-602 pubmed
    ..Negation of ras-induced senescence may be relevant during multistep tumorigenesis. ..
  65. Ralhan R, Agarwal S, Mathur M, Wasylyk B, Srivastava A. Association between polymorphism in p21(Waf1/Cip1) cyclin-dependent kinase inhibitor gene and human oral cancer. Clin Cancer Res. 2000;6:2440-7 pubmed
    The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellular growth arrest, terminal differentiation, and apoptosis...
  66. Sherr C. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 2000;60:3689-95 pubmed
    ..Lesions in the p16--cyclin D-CDK4--Rb and ARF--Mdm2--p53 pathways occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of most, if not all, cancer cells. ..
  67. Huang J, Chuang L, Guh J, Chen C, Yang Y, Chiang T, et al. Effect of nitric oxide-cGMP-dependent protein kinase activation on advanced glycation end-product-induced proliferation in renal fibroblasts. J Am Soc Nephrol. 2005;16:2318-29 pubmed
    ..Furthermore, induction of NO-PKG significantly increased p21Waf1/Cip1 expression in AGE-treated NRK-49F cells...
  68. Zhou H, Fujigaki Y, Kato A, Miyaji T, Yasuda H, Tsuji T, et al. Inhibition of p21 modifies the response of cortical proximal tubules to cisplatin in rats. Am J Physiol Renal Physiol. 2006;291:F225-35 pubmed
    ..Because antisense may not adequately be taken up and/or function in PTs in the OSOM, the role of p21 in PTs in the OSOM in CDDP-induced ARF remains to be clarified. ..
  69. Yamamoto S, Kohsaka S, Nakajima K. Role of cell cycle-associated proteins in microglial proliferation in the axotomized rat facial nucleus. Glia. 2012;60:570-81 pubmed publisher
  70. Witko Sarsat V, Canteloup S, Durant S, Desdouets C, Chabernaud R, Lemarchand P, et al. Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation. J Biol Chem. 2002;277:47338-47 pubmed the proliferation of myeloid cells via the proteolytic regulation of the cyclin-dependent kinase inhibitor p21(waf1)...
  71. Heatley G, Kiland J, Faha B, Seeman J, Schlamp C, Dawson D, et al. Gene therapy using p21WAF-1/Cip-1 to modulate wound healing after glaucoma trabeculectomy surgery in a primate model of ocular hypertension. Gene Ther. 2004;11:949-55 pubmed
    ..Results show that eyes treated with p21 exhibited open surgical ostomies by both functional and histological criteria, and did not display any side effects seen in control animals that were treated with MMC. ..
  72. Baldursson B, Syrjanen S, Beitner H. Expression of p21WAF1/CIP1, p53, bcl-2 and Ki-67 in venous leg ulcers with and without squamous cell carcinoma. Acta Derm Venereol. 2000;80:251-5 pubmed
    ..There was no perilesional p53 or p21 activity in the cancer samples. The results regarding perilesional expression are different from those reported in UV-induced squamous cell carcinomas and probably reflect a different carcinogen. ..
  73. Gomes W, Kessler J. Msx-2 and p21 mediate the pro-apoptotic but not the anti-proliferative effects of BMP4 on cultured sympathetic neuroblasts. Dev Biol. 2001;237:212-21 pubmed
    ..treatment induces expression of the transcription factor Msx-2 and the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) (p21)...
  74. Xaus J, Besalduch N, Comalada M, Marcoval J, Pujol R, Mana J, et al. High expression of p21 Waf1 in sarcoid granulomas: a putative role for long-lasting inflammation. J Leukoc Biol. 2003;74:295-301 pubmed
    ..We have described that interferon-gamma (IFN-gamma) inhibits apoptosis in macrophages through the expression of p21(Waf1). Here, we explore the molecular mechanisms involved in the inhibition of apoptosis in sarcoid granulomas...
  75. Pan D, Ke Y, Liu W, Wei Y, Tang J, Cao H. [Platelet-derived growth factor-BB inhibited p21(WAF1) expression partially through transforming growth factor-beta signalling system in vascular smooth muscle cell]. Zhonghua Xin Xue Guan Bing Za Zhi. 2010;38:160-5 pubmed
    To assess if the modulating effect of platelet-derived growth factor (PDGF)-BB on p21(WAF1) was mediated by upregulating transforming growth factor (TGF)-beta(1) expression in vascular smooth muscle cells (VSMC)...
  76. Scholpa N, Zhang X, Kolli R, Cummings B. Epigenetic changes in p21 expression in renal cells after exposure to bromate. Toxicol Sci. 2014;141:432-40 pubmed publisher
    ..Collectively, these data show the novel finding that KBrO3-induced renal cell death is altered by inhibitors of epigenetic modifying enzymes and that KBrO3 itself induces epigenetic changes in the p21 gene. ..
  77. Driver K, Song H, Lesueur F, Ahmed S, Barbosa Morais N, Tyrer J, et al. Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population. Carcinogenesis. 2008;29:333-41 pubmed publisher
    ..tag SNPs were used to evaluate 240 common SNPs found in the genes: CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKNIB, CDKN2A/CDKN2B, CDKN2C and CDKN2D...
  78. Li M, Li Z, Sun X, Yang L, Fang P, Liu Y, et al. Heme oxygenase-1/p21WAF1 mediates peroxisome proliferator-activated receptor-gamma signaling inhibition of proliferation of rat pulmonary artery smooth muscle cells. FEBS J. 2010;277:1543-50 pubmed publisher
    ..In addition, rosiglitazone stimulated p21(WAF1) expression in PASMCs, a 2...
  79. Yamada K, Tamamori Adachi M, Goto I, Iizuka M, Yasukawa T, Aso T, et al. Degradation of p21Cip1 through anaphase-promoting complex/cyclosome and its activator Cdc20 (APC/CCdc20) ubiquitin ligase complex-mediated ubiquitylation is inhibited by cyclin-dependent kinase 2 in cardiomyocytes. J Biol Chem. 2011;286:44057-66 pubmed publisher
    ..Our study provides a novel insight on the control of p21Cip1 by ubiquitin-mediated degradation and its implication in cell cycle arrest in terminal differentiation. ..
  80. Kilarkaje N, Al Bader M. Diabetes-induced oxidative DNA damage alters p53-p21CIP1/Waf1 signaling in the rat testis. Reprod Sci. 2015;22:102-12 pubmed publisher
    ..of p53 and protein 21(cyclin-dependent kinase interacting protein 1/wild-type p53-activated factor 1) (p21(CIP1/Waf1)) in both diabetic groups did not show any time-dependent effects but occurred concurrent with an upregulation of p-..
  81. Hong F, Zhang A, Huang X, Liu Z. [The expression of P16, P21(WAF1/CIP1) and Cyclin D1 proteins in skin of patients with arseniasis caused by coal-burning and their significance]. Zhonghua Yu Fang Yi Xue Za Zhi. 2000;34:324-6 pubmed
    To study the relationships between arseniasis and skin carcinoma. The expressions of p16, p21(WAF1/CIP1) and Cyclin D1 proteins in skin of arsenic intoxication patients caused by coal-burning was measured by immunohistochemistry methods...
  82. Peschos D, Tsanou E, Stefanou D, Damala C, Vougiouklakis T, Mitselou A, et al. Expression of cyclin-dependent kinases inhibitors p21(WAF1) and p27(KIP1) in benign, premalignant and malignant laryngeal lesions. correlation with cell cycle regulatory proteins. In Vivo. 2004;18:719-24 pubmed
    ..05). Due to the increased expression levels of CDKIs in laryngeal carcinomas, we suggest the existence of a mechanism by which tumor cells tolerate the inhibitory effect of these proteins on cell cycle progression. ..
  83. Mitsuhashi J, Mikami T, Saigenji K, Okayasu I. Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p21 expression in rectal mucosa and neoplastic development. Pathol Int. 2005;55:113-21 pubmed
    ..An immunohistochemical examination of Ki-67, p53, p21(WAF1) and ssDNA labeling was also included...
  84. Hauck L, Harms C, Grothe D, An J, Gertz K, Kronenberg G, et al. Critical role for FoxO3a-dependent regulation of p21CIP1/WAF1 in response to statin signaling in cardiac myocytes. Circ Res. 2007;100:50-60 pubmed
    ..We investigated the role of the cell cycle inhibitor p21(CIP1/WAF1) (p21) in statin-dependent inhibition of hypertrophic growth in postmitotic cardiomyocytes...
  85. Nakaya N, Hemish J, Krasnov P, Kim S, Stasiv Y, Michurina T, et al. noxin, a novel stress-induced gene involved in cell cycle and apoptosis. Mol Cell Biol. 2007;27:5430-44 pubmed
    ..Our results suggest that Noxin may be a component of the cell defense system: it is activated by various stress stimuli, helps cells to withdraw from cycling, and opposes apoptosis. ..
  86. Laub F, Lei L, Sumiyoshi H, Kajimura D, Dragomir C, Smaldone S, et al. Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. Mol Cell Biol. 2005;25:5699-711 pubmed
    ..KLF7 activity might therefore control neuronal morphogenesis in part by optimizing the levels of molecules that promote axon outgrowth. ..
  87. Pang H, Wen Y, Ma N, Wang Y, Shi L. Protective role of a novel erythrocyte-derived depressing factor on blood vessels of renovascular hypertensive rats. Clin Exp Pharmacol Physiol. 2007;34:393-8 pubmed
    ..In addition, EDDF inhibited the phosphorylation of ERK1/2 and decreased the expression of cyclin D1 and CDK4; p21 (Cip1) levels were increased after treatment with EDDF. 4...
  88. Altavilla G, Staffieri A, Busatto G, Canesso A, Giacomelli L, Marioni G. Expression of p53, p16INK4A, pRb, p21WAF1/CIP1, p27KIP1, cyclin D1, Ki-67 and HPV DNA in sinonasal endophytic Schneiderian (inverted) papilloma. Acta Otolaryngol. 2009;129:1242-9 pubmed publisher
    ..Twenty SIPs were evaluated for p53, p16(INK4a), pRb, p21(WAF1), p27(Kip1), cyclin D1 and Ki-67 expression by immunohistochemistry...
  89. Zhang X, Zhou D, Strakovsky R, Zhang Y, Pan Y. Hepatic cellular senescence pathway genes are induced through histone modifications in a diet-induced obese rat model. Am J Physiol Gastrointest Liver Physiol. 2012;302:G558-64 pubmed publisher
    ..analysis demonstrated a significant increase of both the amount and the transcription rates of p16(INK4a) and p21(Cip1) mRNA in OP rats...
  90. Wu W, Liu Q, Liu Y, Yu Z, Wang Y. Dixdc1 targets CyclinD1 and p21 via PI3K pathway activation to promote Schwann cell proliferation after sciatic nerve crush. Biochem Biophys Res Commun. 2016;478:956-63 pubmed publisher
    ..In summary, these data demonstrated that Dixdc1 might participate in Schwann cell proliferation by targeting CyclinD1 and p21 at least partially through the PI3K/AKT activation. ..
  91. Trotter M, Tang L, Tron V. Overexpression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in human cutaneous malignant melanoma. J Cutan Pathol. 1997;24:265-71 pubmed
    p21(WAF1/CIP1) (p21) is an inhibitor of cyclin-dependent kinases recently identified as the downstream effector of wild-type p53-mediated cell cycle arrest...
  92. Nibu K, Yanagisawa A, Nakamizo M, Hoki K, Nigauri T, Kawabata K, et al. Clinical role of p53 and p21WAF1/CIP1 in squamous cell carcinoma of the pyriform sinus. Acta Otolaryngol. 1998;118:432-7 pubmed
    To investigate the clinical significance of p53 and p21WAF1/CIP1 in the advanced squamous cell carcinoma (SCC) of the pyriform sinus, we performed immunohistochemical staining of p53 and p21WAF1/CIP1 on the biopsy specimens from patients ..