Cdkn2a

Summary

Gene Symbol: Cdkn2a
Description: cyclin-dependent kinase inhibitor 2A
Alias: Arf, INK4A, MTS1, p16, p16Cdkn2a, p19ARF, cyclin-dependent kinase inhibitor 2A, CDK4I, Cyclin dependent kinase inhibitor 2A (p16, inhibits CDK4), alternative reading frame, cdkn2a, cell cycle inhibitor, cell cycle regulator, cyclin-dependent kinase 4 inhibitor A, cyclin-dependent kinase inhibitor 2a p16Ink4a, cyclin-dependent kinase inhibitor 2a p19Arf, p16-INK4, p16-INK4a
Species: rat
Products:     Cdkn2a

Top Publications

  1. Yao Q, He X, Zhang J, He J. [Promotor hypermethylation of E-cadherin, p16 and estrogen receptor in prostate carcinoma]. Zhonghua Nan Ke Xue. 2006;12:28-31 pubmed
    To investigate promotor hypermethylation of the CpG islands of E-Cadherin, p16 and estrogen receptor (ER) in prostate carcinoma and explore whether such methylation might play a role in the tumorigenesis and malignant progression of ..
  2. Robinson Bennett B, Belch R, Han A. Loss of p16 in recurrent malignant mixed müllerian tumors of the uterus. Int J Gynecol Cancer. 2006;16:1354-7 pubmed
    ..Five cases of recurrent uterine MMMT were examined by paraffin immunohistochemistry for the expression of p53, p16, P-cadherin, and Cerb-B2...
  3. Buchynska L, Nesina I. Expression of the cell cycle regulators p53, p21(WAF1/CIP1) and p16(INK4a) in human endometrial adenocarcinoma. Exp Oncol. 2006;28:152-5 pubmed
    To study correlation links between expression level of proteins p53, p21(WAF1/CIP), p16(INK4) and proliferative potential in human endometrial adenocarcinoma (EC)...
  4. Hong Y, Yang L, Li C, Xia H, Rhodus N, Cheng B. Frequent mutation of p16(CDKN2A) exon 1 during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. Mol Carcinog. 2007;46:85-90 pubmed
    ..Twenty mutations, including a missense mutation of the start codon resulting in alternative reading frame of p16(CDKN2A) exon 1, were also identified...
  5. O Neill C, McBride H, Connolly L, Deavers M, Malpica A, McCluggage W. High-grade ovarian serous carcinoma exhibits significantly higher p16 expression than low-grade serous carcinoma and serous borderline tumour. Histopathology. 2007;50:773-9 pubmed
    ..The aim of this study was to compare expression of p16 INK4A (p16) in these two tumour types...
  6. Bai H, Gu L, Zhou J, Deng D. p16 hypermethylation during gastric carcinogenesis of Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine. Mutat Res. 2003;535:73-8 pubmed
    Inactivation of the tumor suppressor gene, p16 by CpG hypermethylation is a common event in various tumors including gastric carcinoma...
  7. Krishnamurthy J, Torrice C, Ramsey M, Kovalev G, Al Regaiey K, Su L, et al. Ink4a/Arf expression is a biomarker of aging. J Clin Invest. 2004;114:1299-307 pubmed
    The Ink4a/Arf locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which are principal mediators of cellular senescence...
  8. Bruggeman S, Valk Lingbeek M, van der Stoop P, Jacobs J, Kieboom K, Tanger E, et al. Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. Genes Dev. 2005;19:1438-43 pubmed
    The Polycomb group (PcG) gene Bmi1 promotes cell proliferation and stem cell self-renewal by repressing the Ink4a/Arf locus...
  9. Colombo E, Bonetti P, Lazzerini Denchi E, Martinelli P, Zamponi R, Marine J, et al. Nucleophosmin is required for DNA integrity and p19Arf protein stability. Mol Cell Biol. 2005;25:8874-86 pubmed
    Nucleophosmin (NPM) is a nucleolar phosphoprotein that binds the tumor suppressors p53 and p19(Arf) and is thought to be indispensable for ribogenesis, cell proliferation, and survival after DNA damage...

More Information

Publications104 found, 100 shown here

  1. Bagnyukova T, Tryndyak V, Montgomery B, Churchwell M, Karpf A, James S, et al. Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene. Carcinogenesis. 2008;29:638-46 pubmed publisher
    ..nucleotide element-1-associated histone H4 lysine 20 trimethylation, as well as hypermethylation of the p16(INK4A) gene. These epigenetic changes were not observed in the livers of female rats or the kidneys of both sexes...
  2. Suzuki H, Kurita M, Mizumoto K, Moriyama M, Aiso S, Nishimoto I, et al. The ARF tumor suppressor inhibits BCL6-mediated transcriptional repression. Biochem Biophys Res Commun. 2005;326:242-8 pubmed
    The ARF tumor suppressor gene antagonizes generation of various tumors. ARF-mediated tumor suppression occurs in a p53-independent manner as well as in a p53-dependent manner...
  3. Shank Calvo J, Draheim K, Bhasin M, Kelliher M. p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice. Oncogene. 2006;25:3023-31 pubmed
    Analysis of the INK4A/ARF locus in human T-ALL patients revealed frequent deletions in exon 2, the exon common to both p16(INK4A) and p14(ARF)...
  4. Natrajan R, Warren W, Messahel B, Reis Filho J, Brundler M, Dome J, et al. Complex patterns of chromosome 9 alterations including the p16INK4a locus in Wilms tumours. J Clin Pathol. 2008;61:95-102 pubmed
    Previous data implicating genetic and epigenetic events on chromosome 9, including the CDKN2A/2B locus, as molecular predictors of Wilms tumour relapse, have been conflicting...
  5. de Koning M, Quint W, Pirog E. Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma. Mod Pathol. 2008;21:334-44 pubmed publisher
    ..The HPV 16 intratypic variation showed correlation with patients' ethnic background. P16INK4a immunostaining seems to be a sensitive and specific marker of vulvar carcinomas positive for oncogenic mucosal HPVs. ..
  6. Zhang Y, Xiong Y. Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53. Mol Cell. 1999;3:579-91 pubmed
    The mammalian ARF-INK4a locus uniquely encodes two cell cycle inhibitors by using separate promoters and alternative reading frames. p16INK4a maintains the retinoblastoma protein in its growth suppressive state while ARF stabilizes p53...
  7. Sugimoto M, Kuo M, Roussel M, Sherr C. Nucleolar Arf tumor suppressor inhibits ribosomal RNA processing. Mol Cell. 2003;11:415-24 pubmed
    The p19(Arf) tumor suppressor, a nucleolar protein, binds to Mdm2 to induce p53-dependent cell cycle arrest. Arf also prevents the proliferation of cells lacking Mdm2 and p53, albeit less efficiently...
  8. Eliason M, Larson A, Florell S, Zone J, Cannon Albright L, Samlowski W, et al. Population-based prevalence of CDKN2A mutations in Utah melanoma families. J Invest Dermatol. 2006;126:660-6 pubmed
    Cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) is the major melanoma predisposition gene...
  9. Cheong C, Sung Y, Lee J, Choi Y, Song J, Kee C, et al. Role of INK4a locus in normal eye development and cataract genesis. Mech Ageing Dev. 2006;127:633-8 pubmed
    The murine INK4a locus encodes the critical tumor suppressor proteins, p16(INK4a) and p19(ARF). Mice lacking both p16(INK4a) and p19(ARF) (INK4a-/-) in their FVB/NJ genetic backgrounds developed cataracts and microophthalmia...
  10. Adamovic T, Hamta A, Roshani L, Lü X, Röhme D, Helou K, et al. Rearrangement and allelic imbalance on chromosome 5 leads to homozygous deletions in the CDKN2A/2B tumor suppressor gene region in rat endometrial cancer. Cancer Genet Cytogenet. 2008;184:9-21 pubmed publisher
    ..The copy numbers of loci situated on RNO5 were found to be reduced, particularly for the CDKN2A/2B locus...
  11. Liu W, Liu J, Ao L, Zhou Z, Zhou Y, Cui Z, et al. Dynamic changes in DNA methylation during multistep rat lung carcinogenesis induced by 3-methylcholanthrene and diethylnitrosamine. Toxicol Lett. 2009;189:5-13 pubmed publisher
    ..Remarkably, epigenetic alterations in p16 (CDKN2A), but not in p15 (CDKN2B), were observed, and these correlated with the presence of pathologic lung lesions and ..
  12. Eischen C, Woo D, Roussel M, Cleveland J. Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis. Mol Cell Biol. 2001;21:5063-70 pubmed
    ..Bcl-2 and/or Bcl-X(L) overexpression did not correlate with loss of ARF or p53 function in tumor cells, indicating that these two apoptotic pathways are inactivated independently...
  13. Romanenko A, Morell Quadreny L, Lopez Guerrero J, Pellin A, Nepomnyaschy V, Vozianov A, et al. The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident. Virchows Arch. 2004;445:298-304 pubmed
    ..The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15(INK4B)) in 26 primary renal-cell epithelial tumors from patients with different degrees of ..
  14. Debniak T, Gorski B, Huzarski T, Byrski T, Cybulski C, Mackiewicz A, et al. A common variant of CDKN2A (p16) predisposes to breast cancer. J Med Genet. 2005;42:763-5 pubmed
    A common missense variant of the CDKN2A gene (A148T) predisposes to malignant melanoma in Poland...
  15. Yu J, Zhang S, Saito K, Williams S, Arimura Y, Ma Y, et al. PTEN regulation by Akt-EGR1-ARF-PTEN axis. EMBO J. 2009;28:21-33 pubmed publisher
    ..Here, we describe a novel Akt-EGR1-alternate reading frame (ARF)-PTEN axis, in which PTEN activation in vivo requires p14ARF-mediated sumoylation of EGR1...
  16. Nagao M, Campbell K, Burns K, Kuan C, Trumpp A, Nakafuku M. Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF-p53 pathway. J Cell Biol. 2008;183:1243-57 pubmed publisher
    ..In this study, we show that the protooncoprotein Myc and the tumor suppressor p19(ARF) regulate both NSC self-renewal and their neuronal and glial fate in a developmental stage-dependent manner...
  17. Swafford D, Middleton S, Palmisano W, Nikula K, Tesfaigzi J, Baylin S, et al. Frequent aberrant methylation of p16INK4a in primary rat lung tumors. Mol Cell Biol. 1997;17:1366-74 pubmed
    The p16INK4a (p16) tumor suppressor gene is frequently inactivated by homozygous deletion or methylation of the 5' CpG island in cell lines derived from human non-small-cell lung cancers...
  18. Pogribny I, James S. De novo methylation of the p16INK4A gene in early preneoplastic liver and tumors induced by folate/methyl deficiency in rats. Cancer Lett. 2002;187:69-75 pubmed
    ..model of multistage hepatocarcinogenesis was used to evaluate progressive in vivo changes in p16 promoter methylation in both preneoplastic and tumor tissues...
  19. Gonzalez Navarro H, Abu Nabah Y, Vinue A, Andrés Manzano M, Collado M, Serrano M, et al. p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J Am Coll Cardiol. 2010;55:2258-68 pubmed publisher
    ..the role in atherosclerosis of the tumor suppressor protein ARF (human p14(ARF), mouse p19(ARF)) encoded by the CDKN2A gene...
  20. Treiber N, Maity P, Singh K, Kohn M, Keist A, Ferchiu F, et al. Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue. Aging Cell. 2011;10:239-54 pubmed publisher
    ..Increase in p16(INK4a) , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype...
  21. Sherr C. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 2000;60:3689-95 pubmed
    ..The ARF tumor suppressor, encoded by an alternative reading frame of the INK4a-ARF locus, senses "mitogenic current" flowing through the Rb pathway and is ..
  22. Zhang S, DuBois W, Ramsay E, Bliskovski V, Morse H, Taddesse Heath L, et al. Efficiency alleles of the Pctr1 modifier locus for plasmacytoma susceptibility. Mol Cell Biol. 2001;21:310-8 pubmed
    ..7-centimorgan (cM) chromosomal region that included Cdkn2a, which encodes p16(INK4a) and p19(ARF), and the coding sequences for the BALB/c p16(INK4a) and p19(ARF) alleles ..
  23. 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
    ..primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest...
  24. Louhelainen M, Merasto S, Finckenberg P, Vahtola E, Kaheinen P, Leskinen H, et al. Effects of calcium sensitizer OR-1986 on a cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats. J Physiol Pharmacol. 2009;60:41-7 pubmed
    ..Salt-induced cardiac remodelling was associated with 4-fold increase in cardiac p16(INK4a) mRNA expression, a marker of cellular senescence. OR-1896 dose-dependently ameliorated cardiomyocyte senescence...
  25. Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, et al. Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Lab Invest. 2010;90:360-73 pubmed publisher
    ..SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations...
  26. Medema R, Herrera R, Lam F, Weinberg R. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A. 1995;92:6289-93 pubmed
    ..These data not only show that the presence of pRB is crucial for growth suppression by p16ink4 but also indicate that the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle. ..
  27. Borg A, Sandberg T, Nilsson K, Johannsson O, Klinker M, Masback A, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst. 2000;92:1260-6 pubmed
    Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma...
  28. Kawamoto K, Enokida H, Gotanda T, Kubo H, Nishiyama K, Kawahara M, et al. p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer. Biochem Biophys Res Commun. 2006;339:790-6 pubmed
    ..We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical ..
  29. Kim J, Deluna A, Mungrue I, Vu C, Pouldar D, Civelek M, et al. Effect of 9p21.3 coronary artery disease locus neighboring genes on atherosclerosis in mice. Circulation. 2012;126:1896-906 pubmed publisher
    ..3 locus neighboring genes, including Mtap, the 2 isoforms of Cdkn2a, p16Ink4a and p19Arf, and Cdkn2b, in atherosclerosis using knockout mice models...
  30. Tompkins V, Hagen J, Frazier A, Lushnikova T, Fitzgerald M, Di Tommaso A, et al. A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability. J Biol Chem. 2007;282:1322-33 pubmed
    The ARF tumor suppressor signals through p53 and other poorly defined anti-proliferative pathways to block carcinogenesis...
  31. Volanakis E, Williams R, Sherr C. Stage-specific Arf tumor suppression in Notch1-induced T-cell acute lymphoblastic leukemia. Blood. 2009;114:4451-9 pubmed publisher
    ..hallmarks of T-cell acute lymphoblastic leukemia (T-ALL) include aberrant NOTCH signaling and deletion of the CDKN2A locus, which contains 2 closely linked tumor suppressor genes (INK4A and ARF)...
  32. Zhang J, Zhang J, Li M, Wu Y, Fan Y, Zhou Y, et al. Methylation of RAR-?2, RASSF1A, and CDKN2A genes induced by nickel subsulfide and nickel-carcinogenesis in rats. Biomed Environ Sci. 2011;24:163-71 pubmed publisher
    To investigate the expression variation of RAR-?2, RASSF1A, and CDKN2A gene in the process of nickel-induced carcinogenesis. Nickel subsulfide (Ni(3)S(2)) at dose of 10 mg was given to Wistar rats by intramuscular injection...
  33. Diaz Rodriguez E, Garcia Lavandeira M, Perez Romero S, Senra A, Cañibano C, Palmero I, et al. Direct promoter induction of p19Arf by Pit-1 explains the dependence receptor RET/Pit-1/p53-induced apoptosis in the pituitary somatotroph cells. Oncogene. 2012;31:2824-35 pubmed publisher
    ..We have found a Pit-1 DNA-binding element within the ARF promoter. Pit-1 directly regulates the CDKN2A locus and binds to the p19Arft promoter inducing p19Arf gene expression...
  34. Zheng Y, He L, Wan Y, Song J. H3K9me-enhanced DNA hypermethylation of the p16INK4a gene: an epigenetic signature for spontaneous transformation of rat mesenchymal stem cells. Stem Cells Dev. 2013;22:256-67 pubmed publisher
    ..stem cells (MSCs), changes in senescence-associated molecules, particularly the epigenetic modification of the p16(INK4a) gene, including histone H3 lysine 27/9 methylation (H3K27/9me) and DNA methylation, were investigated in cultured ..
  35. Wolff B, Naumann M. INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene. 1999;18:2663-6 pubmed
    ..In contrast to INK4 proteins, the cell cycle inhibitor p27 enhances NF-kappaB transactivation activity...
  36. Labuhn M, Jones G, Speel E, Maier D, Zweifel C, Gratzl O, et al. Quantitative real-time PCR does not show selective targeting of p14(ARF) but concomitant inactivation of both p16(INK4A) and p14(ARF) in 105 human primary gliomas. Oncogene. 2001;20:1103-9 pubmed
    In many human cancers, the INK4A locus is frequently mutated by homozygous deletions...
  37. Nogueira M, Guedes Neto E, Rosa M, Zettler E, Zettler C. Immunohistochemical expression of p16 and p53 in vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva. Pathol Oncol Res. 2006;12:153-7 pubmed
    This study was undertaken to examine the expression of p16 and p53 in vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma (SCC) of the vulva...
  38. Marsit C, Karagas M, Schned A, Kelsey K. Carcinogen exposure and epigenetic silencing in bladder cancer. Ann N Y Acad Sci. 2006;1076:810-21 pubmed
    ..human bladder cancer (n = 351), the relationship between epigenetic silencing of the tumor-suppressor genes, p16(INK4A), RASSF1A, PRSS3, and the four SFRP genes and exposure to both tobacco and arsenic in bladder cancer...
  39. Normand G, Hemmati P, Verdoodt B, von Haefen C, Wendt J, Güner D, et al. p14ARF induces G2 cell cycle arrest in p53- and p21-deficient cells by down-regulating p34cdc2 kinase activity. J Biol Chem. 2005;280:7118-30 pubmed
    The human INK4a gene locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF). Although primarily proposed to require a functional p53...
  40. Kang S, Kim J, Kim H, Shim J, Nam E, Kim S, et al. Methylation of p16INK4a is a non-rare event in cervical intraepithelial neoplasia. Diagn Mol Pathol. 2006;15:74-82 pubmed
    The cell cycle inhibitor, p16INK4a may be a useful surrogate biomarker of cervical intraepithelial neoplasia (CIN); however, there is currently no consensus of p16INK4a genetic alterations throughout the multiple step process of CIN...
  41. Yin M, Bastacky S, Parwani A, McHale T, Dhir R. p16ink4 immunoreactivity is a reliable marker for urothelial carcinoma in situ. Hum Pathol. 2008;39:527-35 pubmed publisher
    ..Mutations of the cell cycle regulatory gene INK4a (located at 9p21) that encodes p16(INK4) are one of the critical early events in carcinogenesis of UC...
  42. Harashima M, Seki T, Ariga T, Niimi S. Role of p16(INK4a) in the inhibition of DNA synthesis stimulated by HGF or EGF in primary cultured rat hepatocytes. Biomed Res. 2013;34:269-73 pubmed
    In the present study, we investigated the role of p16(INK4a) in the inhibition of DNA synthesis stimulated by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) using RNA interference in primary cultured rat hepatocytes...
  43. Park T, Kim H, Byun K, Jang J, Lee Y, Lim I. Sequential changes in hepatocarcinogenesis induced by diethylnitrosamine plus thioacetamide in Fischer 344 rats: induction of gankyrin expression in liver fibrosis, pRB degradation in cirrhosis, and methylation of p16(INK4A) exon 1 in hepatocellular . Mol Carcinog. 2001;30:138-50 pubmed
    To clarify the sequential changes in pRB and p16 during different stages of hepatocarcinogenesis such as fibrosis, cirrhosis, hepatocellular adenoma (HCA), and hepatocellular carcinoma (HCC), male Fischer 344 rats were singly injected ..
  44. Zhang Y, Sturgis E, Zafereo M, Wei Q, Li G. p14ARF genetic polymorphisms and susceptibility to second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Cancer. 2011;117:1227-35 pubmed publisher
    p14(ARF) , an alternate reading frame (ARF) product of the cyclin-dependent kinase inhibitor 2A locus, plays a critical role in crosstalk between the tumor protein 53 (p53) and retinoblastoma (Rb) pathways and in cellular anticancer ..
  45. Hasan M, Yaguchi T, Sugihara T, Kumar P, Taira K, Reddel R, et al. CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53. J Biol Chem. 2002;277:37765-70 pubmed
    ..locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human)...
  46. Shamanin V, Androphy E. Immortalization of human mammary epithelial cells is associated with inactivation of the p14ARF-p53 pathway. Mol Cell Biol. 2004;24:2144-52 pubmed
    Inactivation of the ARF-p53 tumor suppressor pathway leads to immortalization of murine fibroblasts. The role of this pathway in immortalization of human epithelial cells is not clear...
  47. Toncheva D, Zaharieva B. Coexistence of copy number changes of different genes (INK4A, erbB-1, erbB-2, CMYC, CCND1 and ZNF217) in urothelial tumors. Tumour Biol. 2005;26:88-93 pubmed
    The aim of this study was to establish the frequency of combinatorial and separate copy number changes of INK4A (9p21), erbB-1 (7p11), erbB-2 (17q17-21), CMYC (8q24), CCND1 (11q13) and ZNF217 (20q13) in urothelial tumors; a tissue ..
  48. Focchi G, Silva I, Nogueira de Souza N, Dobo C, Oshima C, Stávale J. Immunohistochemical expression of p16(INK4A) in normal uterine cervix, nonneoplastic epithelial lesions, and low-grade squamous intraepithelial lesions. J Low Genit Tract Dis. 2007;11:98-104 pubmed
    In this study, the authors analyzed the immunoexpression of p16 in high-risk human papillomavirus DNA-negative normal and nonneoplastic cervical epithelia, in low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, and ..
  49. Belinsky S, Snow S, Nikula K, Finch G, Tellez C, Palmisano W. Aberrant CpG island methylation of the p16(INK4a) and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. Carcinogenesis. 2002;23:335-9 pubmed
    Recent studies by our laboratory indicate that the p16(INK4a) gene is frequently methylated in lung tumors induced by genotoxic carcinogens and that the frequency for methylation of the estrogen receptor alpha (ER) gene varies as a ..
  50. Narita M, Narita M, Krizhanovsky V, Nũnez S, Chicas A, Hearn S, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell. 2006;126:503-14 pubmed
    ..HMGA proteins cooperate with the p16(INK4a) tumor suppressor to promote SAHF formation and proliferative arrest and stabilize senescence by contributing to ..
  51. Honda R, Yasuda H. Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J. 1999;18:22-7 pubmed
    ..We further investigated whether the tumor suppressor p19(ARF) affects the ubiquitin ligase activity of Mdm2 for p53...
  52. Maloney K, McGavran L, Odom L, Hunger S. Acquisition of p16(INK4A) and p15(INK4B) gene abnormalities between initial diagnosis and relapse in children with acute lymphoblastic leukemia. Blood. 1999;93:2380-5 pubmed
    ..The p16(INK4A) (p16), which encodes for both p16(INK4A) and p19(ARF) proteins, and p15(INK4B) (p15) genes are inactivated by ..
  53. Arcellana Panlilio M, Egeler R, Ujack E, Magliocco A, Stuart G, Robbins S, et al. Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors. Genes Chromosomes Cancer. 2002;35:176-81 pubmed
    ..The status of RB1, INK4A, INK4B, INK4C, INK4D, and ARF in 13 adult and 2 juvenile ovarian GCTs was determined by reverse transcription-..
  54. Bothner B, Aubin Y, Kriwacki R. Peptides derived from two dynamically disordered proteins self-assemble into amyloid-like fibrils. J Am Chem Soc. 2003;125:3200-1 pubmed
    ..The beta-strand-containing fibrils formed from these peptides may allow the directed assembly of decorated fibrils with applications as biological nanostructures. ..
  55. Huang Y, Wu M, Li H. Tumor suppressor ARF promotes non-classic proteasome-independent polyubiquitination of COMMD1. J Biol Chem. 2008;283:11453-60 pubmed publisher
    Although the tumor suppressor ARF is generally accepted for its essential role in activating the p53 pathway, its p53-independent function has also been proposed...
  56. Watari A, Li Y, Higashiyama S, Yutsudo M. A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF. Exp Cell Res. 2012;318:187-95 pubmed publisher
    ..These results indicate that PANO is a new apoptosis-inducing gene by modulating the tumor suppressor protein, p14ARF, and may itself be a new candidate tumor suppressor gene. ..
  57. Taniguchi K, Kohsaka H, Inoue N, Terada Y, Ito H, Hirokawa K, et al. Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis. Nat Med. 1999;5:760-7 pubmed
    ..Thus, the induction of p16INK4a may provide a new approach to the effective treatment of rheumatoid arthritis. ..
  58. Mariappan M, D Silva K, Lee M, Sataranatarajan K, Barnes J, Choudhury G, et al. Ribosomal biogenesis induction by high glucose requires activation of upstream binding factor in kidney glomerular epithelial cells. Am J Physiol Renal Physiol. 2011;300:F219-30 pubmed publisher
    ..High glucose reduced nuclear content of p19ARF and promoted dissolution of inactive UBF-p19ARF complex...
  59. Wang T, Huang M, Hong C, Tse V, Silverberg G, Hsiao M. Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblastoma tumorigenicity in situ. Biochem Biophys Res Commun. 2001;287:173-80 pubmed
    ..this study, the functional expression and efficacy in tumor suppression of 3 tumor suppressor genes (p53, p21, and p16) were tested and compared in a rat GBM cell line (RT-2) after retrovirus mediated gene delivery in vitro and in ..
  60. Tao L, Kramer P, Wang W, Yang S, Lubet R, Steele V, et al. Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents. Carcinogenesis. 2002;23:1447-54 pubmed
    ..In colon tumors relative to the mucosa, the protein and mRNA levels of c-myc were increased, while the levels of p16 and p27 were decreased...
  61. Geradts J, Wilson P. High frequency of aberrant p16(INK4A) expression in human breast cancer. Am J Pathol. 1996;149:15-20 pubmed
    ..p16(INK4A) (16), inhibits phosphorylation of the retinoblastoma protein, pRB, and thus acts as a negative cell cycle regulator. It is inactivated in a wide range of human malignancies, including breast cancer...
  62. Morey S, Smiraglia D, James S, Yu J, Moser M, Foster B, et al. DNA methylation pathway alterations in an autochthonous murine model of prostate cancer. Cancer Res. 2006;66:11659-67 pubmed
    ..Surprisingly, methylation of a downstream exon of p16(INK4a) (p16) was the highest frequency hypermethylation event identified in TRAMP, where it is associated with increased ..
  63. Fasseu M, Aplan P, Chopin M, Boissel N, Bories J, Soulier J, et al. p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis. Blood. 2007;110:2610-9 pubmed
    Inactivation of the CDKN2 genes that encode the p16(INK4A) and p14(ARF) proteins occurs in the majority of human T-cell acute lymphoblastic leukemias (T-ALLs)...
  64. de Torre C, Martínez Escribano J. Novel CDKN2A mutation detected in Spanish melanoma pedigree. Exp Dermatol. 2010;19:e333-5 pubmed publisher
    We have examined alterations in the cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase 4 (CDK4), major melanoma predisposing genes, in a Spanish melanoma-prone population comprising 61 patients from 45 families...
  65. 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
    ..Gene analysis demonstrated a significant increase of both the amount and the transcription rates of p16(INK4a) and p21(Cip1) mRNA in OP rats...
  66. Faderl S, Kantarjian H, Estey E, Manshouri T, Chan C, Rahman Elsaied A, et al. The prognostic significance of p16(INK4a)/p14(ARF) locus deletion and MDM-2 protein expression in adult acute myelogenous leukemia. Cancer. 2000;89:1976-82 pubmed
    The p16(INK4a) locus encodes two distinct proteins, p16(INK4a) and p14(ARF)...
  67. Brummelkamp T, Kortlever R, Lingbeek M, Trettel F, MacDonald M, Van Lohuizen M, et al. TBX-3, the gene mutated in Ulnar-Mammary Syndrome, is a negative regulator of p19ARF and inhibits senescence. J Biol Chem. 2002;277:6567-72 pubmed
    Prolonged culturing of rodent cells in vitro activates p19(ARF) (named p14(ARF) in man), resulting in a p53-dependent proliferation arrest known as senescence...
  68. Hiroyasu M, Ozeki M, Kohda H, Echizenya M, Tanaka T, Hiai H, et al. Specific allelic loss of p16 (INK4A) tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am J Pathol. 2002;160:419-24 pubmed
    Oxidative tissue damage has been shown to be associated with carcinogenesis. In human cancers p16(INK4A) is one of the most frequently mutated tumor suppressor genes...
  69. Kannan K, Sharpless N, Xu J, O Hagan R, Bosenberg M, Chin L. Components of the Rb pathway are critical targets of UV mutagenesis in a murine melanoma model. Proc Natl Acad Sci U S A. 2003;100:1221-5 pubmed
    ..Moreover, UV-induced melanomas showed a strict reciprocal relationship between cdk6 amplification and p16(INK4a) loss, which is consistent with the actions of UV along the Rb pathway...
  70. Bond J, Jones C, Haughton M, deMicco C, Kipling D, Wynford Thomas D. Direct evidence from siRNA-directed "knock down" that p16(INK4a) is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation. Exp Cell Res. 2004;292:151-6 pubmed
    The selective pressure for disruption of the cyclin-dependent kinase inhibitor p16(INK4a) in human cancer has been postulated to reflect its role in mediating growth arrest, both in response to telomere erosion (replicative senescence) ..
  71. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista D, Gejman R, et al. Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 2007;282:24731-42 pubmed
    ..These data suggest that MEG3 non-coding RNA may function as a tumor suppressor, whose action is mediated by both p53-dependent and p53-independent pathways. ..
  72. Mitrea D, Grace C, Buljan M, Yun M, Pytel N, Satumba J, et al. Structural polymorphism in the N-terminal oligomerization domain of NPM1. Proc Natl Acad Sci U S A. 2014;111:4466-71 pubmed publisher
    ..We propose that the diverse functional repertoire associated with NPM1 is controlled through a regulated unfolding mechanism signaled through posttranslational modifications and intermolecular interactions...
  73. Chien W, Catallo R, Chebel A, Baranger L, Thomas X, Béné M, et al. The p16(INK4A)/pRb pathway and telomerase activity define a subgroup of Ph+ adult Acute Lymphoblastic Leukemia associated with inferior outcome. Leuk Res. 2015;39:453-61 pubmed publisher
    ..The p16(INK4A)/CDK4-6/pRb pathway and telomerase activity, which are implicated in cell activation and aging, were analyzed to ..
  74. Monsonego J, Pollini G, Evrard M, Sednaoui P, Monfort L, Quinzat D, et al. P16(INK4a) immunocytochemistry in liquid-based cytology samples in equivocal Pap smears: added value in management of women with equivocal Pap smear. Acta Cytol. 2007;51:755-66 pubmed
    To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears...
  75. Westhoff J, Hilgers K, Steinbach M, Hartner A, Klanke B, Amann K, et al. Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. Hypertension. 2008;52:123-9 pubmed publisher
    ..b>Cell cycle inhibitor p16(INK4a) is the key mediator for stress and aberrant signaling induced senescence...
  76. Horn H, Vousden K. Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway. Oncogene. 2008;27:5774-84 pubmed publisher
    ..These include the alternate reading frame (ARF) proteins and the ribosomal proteins L5 and L11...
  77. Hong Y, Li C, Xia J, Rhodus N, Cheng B. p16(CDKN2A) expression during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. Oral Oncol. 2009;45:640-4 pubmed publisher
    p16(CDKN2A) is one of the most important tumor-suppressor genes and has been investigated widely in recent years for its role in oral carcinogenesis, but few have explored the relationship between its RNA and protein, especially in ..
  78. Nakahara Y, Shintani S, Mihara M, Matsumura T, Hamakawa H. High frequency methylation of p16INK4A gene during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Oncol Rep. 2004;12:101-6 pubmed
    ..Inactivation by hypermethylation of the promoter region of p16INK4A gene was related to carcinogenesis of oral cancer. ..
  79. Benevolo M, Mottolese M, Marandino F, Vocaturo G, Sindico R, Piperno G, et al. Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in cervical low-grade lesions. Mod Pathol. 2006;19:384-91 pubmed
    The p16(INK4a) is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB)...
  80. Vaites L, Lee E, Lian Z, Barbash O, Roy D, Wasik M, et al. The Fbx4 tumor suppressor regulates cyclin D1 accumulation and prevents neoplastic transformation. Mol Cell Biol. 2011;31:4513-23 pubmed publisher
    ..Collectively, these data reveal a requisite role for the SCF(Fbx4) E3 ubiquitin ligase in regulating cyclin D1 accumulation, consistent with tumor suppressive function in vivo. ..
  81. Serrano M, Hannon G, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366:704-7 pubmed
    ..Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D ..
  82. Ogawa K, Tanuma J, Hirano M, Hirayama Y, Semba I, Shisa H, et al. Selective loss of resistant alleles at p15INK4B and p16INK4A genes in chemically-induced rat tongue cancers. Oral Oncol. 2006;42:710-7 pubmed
    ..Accumulation of loss of heterozygosity and methylation of the promoter regions in the tumour suppressor genes in advanced tumours suggests that they may play a role in tongue cancer progression. ..
  83. Wiley A, Katsaros D, Chen H, Rigault de la Longrais I, Beeghly A, Puopolo M, et al. Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential. Cancer. 2006;107:299-308 pubmed
    ..were extracted from fresh frozen tissues and were analyzed for methylation in the promoter region of 6 genes (p16, breast cancer 1 [BRCA1], insulin-like growth factor-binding protein 3 [IGFBP-3], glutathione S-transferase pi 1 [..
  84. Askari M, Sobti R, Nikbakht M, Sharma S. Promoter hypermethylation of tumour suppressor genes (p14/ARF and p16/INK4a): case-control study in North Indian population. Mol Biol Rep. 2013;40:4921-8 pubmed publisher
    ..study, it has been tried to determine the methylation status of two tumour suppressor genes p14/ARF and p16/INK4a in 150 breast cancer patients as well as 150 controls by using MSP-PCR...
  85. Wang J, He X, Luo Y, Yarbrough W. A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2. Biochem J. 2006;393:489-501 pubmed
    The tumour suppressor ARF (alternative reading frame) is encoded by the INK4a (inhibitor of cyclin-dependent kinase 4)/ARF locus, which is frequently altered in human tumours...
  86. Chen J, Huang X, Halicka D, Brodsky S, Avram A, Eskander J, et al. Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol. 2006;290:H1575-86 pubmed
    ..When compared with native collagen, early passage HUVECs showed increased p53, p21(CIP1) (p21), and p16(INK4a) (p16) mRNA expression after exposure to GC...
  87. Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K, Mori T, et al. Reduced expression of INK4a/ARF genes in stem-like sphere cells from rat sarcomas. Biochem Biophys Res Commun. 2007;362:773-8 pubmed
    ..Interestingly, spheres from both sarcomas remarkably decreased the expression of INK4a/ARF locus genes, p16(INK4a) and p19(ARF), which could be related to the resistance against cell senescence and ..
  88. Gannon B, Manduch M, Childs T. Differential Immunoreactivity of p16 in leiomyosarcomas and leiomyoma variants. Int J Gynecol Pathol. 2008;27:68-73 pubmed
    ..include insulinlike growth factor 1, h-caldesmon, cytokeratin 18, and the cyclin-dependent kinase 4 inhibitor, p16. To determine whether the immunohistochemical expression of these proteins could aid in the diagnosis of LMS and LM ..
  89. Watanabe G, Pena P, Shambaugh G, Haines G, Pestell R. Regulation of cyclin dependent kinase inhibitor proteins during neonatal cerebella development. Brain Res Dev Brain Res. 1998;108:77-87 pubmed
    ..p27 increased 20-fold between days 4 and 24, whereas p21 rose twofold between 6 to 11 days. p19, p18 and p16 increased approximately two- to threefold, falling to low levels in the adult...
  90. Hashemi J, Linder S, Platz A, Hansson J. Melanoma development in relation to non-functional p16/INK4A protein and dysplastic naevus syndrome in Swedish melanoma kindreds. Melanoma Res. 1999;9:21-30 pubmed
    The CDKN2A gene encodes the cell cycle inhibitor p16/ INK4A, which is involved in familial cutaneous melanoma...
  91. Maloney K, Rubnitz J, Cleary M, Frankel L, Hakami N, Link M, et al. Lack of ETV6 (TEL) gene rearrangements or p16INK4A/p15INK4B homozygous gene deletions in infant acute lymphoblastic leukemia. Leukemia. 1997;11:979-83 pubmed
    ..described molecular abnormalities in childhood ALL are ETV6 gene rearrangements and homozygous deletions of p16(INK4A) and/or p15(INK4B)...
  92. Woods Y, Xirodimas D, Prescott A, Sparks A, Lane D, Saville M. p14 Arf promotes small ubiquitin-like modifier conjugation of Werners helicase. J Biol Chem. 2004;279:50157-66 pubmed
    Here we demonstrate a novel p53-independent interaction between the nucleolar tumor suppressors, p14 Arf and Werners helicase (WRN). Binding of p14 Arf to WRN is multivalent and resembles the binding of p14 Arf to Mdm2...