p16

Summary

Gene Symbol: p16
Description: cyclin dependent kinase inhibitor 2A
Alias: ARF, CDK4I, CDKN2, CMM2, INK4, INK4A, MLM, MTS-1, MTS1, P14, P14ARF, P16, P16-INK4A, P16INK4, P16INK4A, P19, P19ARF, TP16, cyclin-dependent kinase inhibitor 2A, CDK4 inhibitor p16-INK4, alternative reading frame, cell cycle negative regulator beta, cyclin-dependent kinase 4 inhibitor A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4), multiple tumor suppressor 1
Species: human
Products:     p16

Top Publications

  1. Zhang Y, Xiong Y, Yarbrough W. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell. 1998;92:725-34 pubmed
    The INK4a-ARF locus encodes two unrelated proteins that both function in tumor suppression. p16INK4 binds to and inhibits the activity of CDK4 and CDK6, and ARF arrests the cell cycle in a p53-dependent manner...
  2. Jung A, Briolat J, Millon R, de Reyniès A, Rickman D, Thomas E, et al. Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma. Int J Cancer. 2010;126:1882-1894 pubmed publisher
  3. Demenais F, Mohamdi H, Chaudru V, Goldstein A, Newton Bishop J, Bishop D, et al. Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study. J Natl Cancer Inst. 2010;102:1568-83 pubmed publisher
    ..Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings. ..
  4. Zhao N, Ang M, Yin X, Patel M, Fritchie K, Thorne L, et al. Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer. Br J Cancer. 2012;107:482-90 pubmed publisher
    ..human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible...
  5. Yang X, Pfeiffer R, Wheeler W, Yeager M, Chanock S, Tucker M, et al. Identification of modifier genes for cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations. Int J Cancer. 2009;125:2912-7 pubmed publisher
    ..Our findings support the hypothesis that common genetic polymorphisms in DNA repair, apoptosis and immune response pathways may modify the risk of CMM in CMM-prone families with or without CDKN2A mutations. ..
  6. Hribal M, Presta I, Procopio T, Marini M, Stancakova A, Kuusisto J, et al. Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B. Diabetologia. 2011;54:795-802 pubmed publisher
  7. Freathy R, Bennett A, Ring S, Shields B, Groves C, Timpson N, et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes. 2009;58:1428-33 pubmed publisher
    ..Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype. ..
  8. Yang X, Liang X, Pfeiffer R, Wheeler W, Maeder D, Burdette L, et al. Associations of 9p21 variants with cutaneous malignant melanoma, nevi, and pigmentation phenotypes in melanoma-prone families with and without CDKN2A mutations. Fam Cancer. 2010;9:625-33 pubmed publisher
    ..These genetic variants may, at least partially, exert their effects through nevi and tanning ability. ..
  9. Vivo M, Ranieri M, Sansone F, Santoriello C, Calogero R, Calabrò V, et al. Mimicking p14ARF phosphorylation influences its ability to restrain cell proliferation. PLoS ONE. 2013;8:e53631 pubmed publisher
    ..Here, we show for the first time that p14ARF is a PKC target...

More Information

Publications402 found, 100 shown here

  1. Bishop D, Demenais F, Iles M, Harland M, Taylor J, Corda E, et al. Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet. 2009;41:920-5 pubmed publisher
    ..Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk. ..
  2. Kordi Tamandani D, Moazeni Roodi A, Rigi Ladez M, Hashemi M, Birjandian E, Torkamanzehi A. Analysis of methylation patterns and expression profiles of p14ARF gene in patients with oral squamous cell carcinoma. Int J Biol Markers. 2010;25:99-103 pubmed
    To analyze the promoter methylation profile and mRNA expression of the p14ARF gene in oral squamous cell carcinoma (OSCC).
  3. Haferkamp S, Becker T, Scurr L, Kefford R, Rizos H. p16INK4a-induced senescence is disabled by melanoma-associated mutations. Aging Cell. 2008;7:733-45 pubmed
    The p16(INK4a)-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression...
  4. Hwang H, Tse C, Rodriguez S, Gown A, Churg A. p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma. Am J Surg Pathol. 2014;38:681-8 pubmed publisher
    ..Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in ..
  5. Helgadottir H, Höiom V, Jonsson G, Tuominen R, Ingvar C, Borg A, et al. High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families. J Med Genet. 2014;51:545-52 pubmed publisher
    ..These cancers were mainly seen in ever-smoking carriers. Germline CDKN2A mutations may confer an increased sensitivity to carcinogens in tobacco smoke. CDKN2A mutation carriers should be counselled to abstain from smoking. ..
  6. Vivo M, Calogero R, Sansone F, Calabro V, Parisi T, Borrelli L, et al. The human tumor suppressor arf interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein. J Biol Chem. 2001;276:14161-9 pubmed
    The INK4a gene, one of the most often disrupted loci in human cancer, encodes two unrelated proteins, p16(INK4a) and p14(ARF) (ARF) both capable of inducing cell cycle arrest...
  7. Skalska L, White R, Franz M, Ruhmann M, Allday M. Epigenetic repression of p16(INK4A) by latent Epstein-Barr virus requires the interaction of EBNA3A and EBNA3C with CtBP. PLoS Pathog. 2010;6:e1000951 pubmed publisher
    As an inhibitor of cyclin-dependent kinases, p16(INK4A) is an important tumour suppressor and inducer of cellular senescence that is often inactivated during the development of cancer by promoter DNA methylation...
  8. Cabanillas R, Astudillo A, Valle M, de la Rosa J, Alvarez R, Durán N, et al. Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas. Head Neck. 2013;35:E80-4 pubmed publisher
    ..Germline mutations in the CDKN2A locus, encoding the key tumor suppressor proteins p16/INK4A and p14/ARF, are frequently present in kindreds with hereditary cutaneous melanoma but have seldom been reported ..
  9. Pomerantz J, Schreiber Agus N, Liegeois N, Silverman A, Alland L, Chin L, et al. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell. 1998;92:713-23 pubmed
    The INK4a gene encodes two distinct growth inhibitors--the cyclin-dependent kinase inhibitor p16Ink4a, which is a component of the Rb pathway, and the tumor suppressor p19Arf, which has been functionally linked to p53...
  10. Groenewoud M, Dekker J, Fritsche A, Reiling E, Nijpels G, Heine R, et al. Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps. Diabetologia. 2008;51:1659-63 pubmed publisher
    ..Our results, based on hyperglycaemic clamps, provide further insight into the pathogenic mechanism behind the association of these gene variants with type 2 diabetes. ..
  11. Zhang C, Guo X, Zhang L, Lu Z, Ma N, Cheng Y, et al. Methylation-related silencing of p14ARF gene correlates with telomerase activity and mRNA expression of human telomerase reverse transcriptase in hepatocellular carcinoma. J Surg Oncol. 2008;98:462-8 pubmed publisher
    The p14(ARF) gene encodes a critical negative regulator of cell cycle progression. And upregulation of telomerase activity has been considered a critical step to tumors...
  12. He J, Qiao J, Zhu H. p14ARF promoter region methylation as a marker for gliomas diagnosis. Med Oncol. 2011;28:1218-24 pubmed publisher
    ..Herein, we studied the methylation status in the promoter region of the p14ARF tumor suppressor gene in 33 brain tissues isolated from glioma patients (astrocytomas) and compared to 12 brain ..
  13. Nakayama G, Hibi K, Kodera Y, Koike M, Fujiwara M, Nakao A. P16 methylation in serum as a potential marker for the malignancy of colorectal carcinoma. Anticancer Res. 2007;27:3367-70 pubmed
    The aim of the present study was to determine if p16 methylation in the serum can serve as a candidate marker for the malignancy of colorectal carcinoma, real-time quantitative methylation-specific PCR (RTQ-MSP) was performed for p16 ..
  14. Bodner K, Laubichler P, Kimberger O, Czerwenka K, Zeillinger R, Bodner Adler B. Expression of p16 protein and epidermal growth factor receptor in patients with adenocarcinoma of the uterine cervix: an immunohistochemical analysis. Arch Gynecol Obstet. 2011;283:611-6 pubmed publisher
    The present study assessed the expression of p16 and epidermal growth factor receptor (EGFR) in patients with adenocarcinoma of the uterine cervix to determine their influence on prognosis and to evaluate a possible association between ..
  15. Chen J, Chen Y, Wang Y, Tseng R, Chen C, Wang Y. Alterations of the p16(ink4a) gene in resected nonsmall cell lung tumors and exfoliated cells within sputum. Int J Cancer. 2002;98:724-31 pubmed
    ..5% of 107 resected nonsmall cell lung cancers (NSCLCs), suggesting that the p16(INK4a) gene is frequently inactivated in primary NSCLC...
  16. Brookes S, Rowe J, Ruas M, Llanos S, Clark P, Lomax M, et al. INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. EMBO J. 2002;21:2936-45 pubmed
    The CDKN2A tumour suppressor locus encodes two distinct proteins, p16(INK4a) and p14(ARF), both of which have been implicated in replicative senescence, the state of permanent growth arrest provoked in somatic cells by aberrant ..
  17. Takeuchi F, Serizawa M, Yamamoto K, Fujisawa T, Nakashima E, Ohnaka K, et al. Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes. 2009;58:1690-9 pubmed publisher
    ..The strength of association was more prominent in the Japanese population than in Europeans for more than half of the confirmed type 2 diabetes loci. ..
  18. Chen D, Kon N, Li M, Zhang W, Qin J, Gu W. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell. 2005;121:1071-83 pubmed
    Although the importance of the ARF tumor suppressor in p53 regulation is well established, numerous studies indicate that ARF also suppresses cell growth in a p53/Mdm2-independent manner...
  19. 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...
  20. Zadeh M, Amini R, Firoozray M, Derakhshandeh Peykar P. Frequent homozygous deletion of p16/CDKN2A gene in malignant gliomas of Iranian patients. Pak J Biol Sci. 2007;10:4246-50 pubmed
    ..6%) of glioblastoma multiforme, in total 26 out of 40 cases (65%) of malignant gliomas. We also found that CDKN2A deleted patients were younger than CDKN2A non-deleted patients and that exon 2 was deleted more than exon 1alpha. ..
  21. Ukpo O, Flanagan J, Ma X, Luo Y, Thorstad W, Lewis J. High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. Am J Surg Pathol. 2011;35:1343-50 pubmed publisher
    ..We constructed tissue microarrays (TMAs) from a cohort of OSCC for which p16 immunohistochemistry and HPV DNA ISH were previously performed on whole sections...
  22. Bilguvar K, Yasuno K, Niemela M, Ruigrok Y, von und zu Fraunberg M, van Duijn C, et al. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008;40:1472-7 pubmed publisher
    ..These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm. ..
  23. Popov N, Gil J. Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health. Epigenetics. 2010;5:685-90 pubmed
    The INK4b-ARF-INK4a locus encodes for two cyclin-dependent kinase inhibitors, p15(INK4b) and p16(INK4a) and a regulator of the p53 pathway, ARF. In addition ANRIL, a non-coding RNA, is also transcribed from the locus...
  24. Qureshi M, Jan N, Dar N, Hussain M, Andrabi K. A novel p16(INK4A) mutation associated with esophageal squamous cell carcinoma in a high risk population. Biomarkers. 2012;17:552-6 pubmed publisher
    This study describes identification of p16(INK4A) sequence variants and their potential association with esophageal squamous cell carcinoma (ESCC) in a high risk population from Kashmir, India...
  25. Rodway H, Llanos S, Rowe J, Peters G. Stability of nucleolar versus non-nucleolar forms of human p14(ARF). Oncogene. 2004;23:6186-92 pubmed
    Fusion proteins containing the amino-terminal domain of human p14(ARF) linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus...
  26. Maruo S, Zhao B, Johannsen E, Kieff E, Zou J, Takada K. Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16INK4A and p14ARF expression. Proc Natl Acad Sci U S A. 2011;108:1919-24 pubmed publisher
    ..We now find that EBNA3C and EBNA3A's essential roles are to repress p16(INK4A) and p14(ARF)...
  27. Kumar R, Smeds J, Berggren P, Straume O, Rozell B, Akslen L, et al. A single nucleotide polymorphism in the 3'untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare. Int J Cancer. 2001;95:388-93 pubmed
    ..in a set of 44 sporadic primary melanomas, which had been earlier analysed for mutations in the CDKN2A (p16/p14(ARF)) gene...
  28. Li Y, Liu L, Tollefsbol T. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J. 2010;24:1442-53 pubmed publisher
    ..restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16(INK4a)...
  29. Gao G, Chernock R, Gay H, Thorstad W, Zhang T, Wang H, et al. A novel RT-PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis. Int J Cancer. 2013;132:882-90 pubmed publisher
    ..Besides HPV16, three other HPV types were also detected, including 33, 35 and 18. Furthermore, HPV and p16 had essentially identical expression signatures, and both HPV and p16 were prognostic biomarkers for the prediction ..
  30. Kannengiesser C, Dalle S, Leccia M, Avril M, Bonadona V, Chompret A, et al. New founder germline mutations of CDKN2A in melanoma-prone families and multiple primary melanoma development in a patient receiving levodopa treatment. Genes Chromosomes Cancer. 2007;46:751-60 pubmed
    ..This observation suggests that there is a need for reconsideration of the hypothesis that levodopa may play a role in melanoma development, at least when in the context of a high-risk genetic background. ..
  31. Veganzones de Castro S, Rafael Fernández S, Vidaurreta Lázaro M, De la Orden V, Mediero Valeros B, Fernández C, et al. p16 gene methylation in colorectal cancer patients with long-term follow-up. Rev Esp Enferm Dig. 2012;104:111-7 pubmed
    b>p16 gene plays an important role in the cell cycle regulation and is considered an important tumor suppressor gene...
  32. Bothner B, Lewis W, DiGiammarino E, Weber J, Bothner S, Kriwacki R. Defining the molecular basis of Arf and Hdm2 interactions. J Mol Biol. 2001;314:263-77 pubmed
    ..In response to hyperproliferative signals, p14(Arf) stabilizes p53 by binding to Hdm2 and inhibits the ubiquitination and subsequent proteosome-dependent ..
  33. Ayrault O, Andrique L, Larsen C, Seite P. Human Arf tumor suppressor specifically interacts with chromatin containing the promoter of rRNA genes. Oncogene. 2004;23:8097-104 pubmed
    The tumor suppressor Arf (Alternative Reading Frame) protein (p14ARF in human and p19ARF in mouse) is mainly located in the nucleolus consistent with its subcellular localization, the protein has been shown to specifically interact with ..
  34. 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
    ..010, P-trend = 0.048). Further large-scale studies are needed to confirm these results. ..
  35. Guney I, Wu S, Sedivy J. Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16(INK4a). Proc Natl Acad Sci U S A. 2006;103:3645-50 pubmed
    ..frequency to a telomere-independent senescent state mediated by the cyclin-dependent kinase inhibitor p16(INK4a)...
  36. Itahana K, Zou Y, Itahana Y, Martinez J, Beausejour C, Jacobs J, et al. Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1. Mol Cell Biol. 2003;23:389-401 pubmed
    The polycomb protein Bmi-1 represses the INK4a locus, which encodes the tumor suppressors p16 and p14(ARF)...
  37. Laud K, Marian C, Avril M, Barrois M, Chompret A, Goldstein A, et al. Comprehensive analysis of CDKN2A (p16INK4A/p14ARF) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma. J Med Genet. 2006;43:39-47 pubmed
    ..However, we identified a p14ARF exon 1beta missense germline mutation (G16D) in a melanoma-neural system tumour syndrome (CMM+NST) family and a ..
  38. Pjanova D, Engele L, Randerson Moor J, Harland M, Bishop D, Newton Bishop J, et al. CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population. Melanoma Res. 2007;17:185-91 pubmed
    ..The detected CDK4 exon 2 mutation was found in only the seventh family identified worldwide with a germline CDK4 mutation. ..
  39. Krakowczyk L, Strzelczyk J, Adamek B, Zalewska Ziob M, Arendt J, Półtorak S, et al. Methylation of the MGMT and p16 genes in sporadic colorectal carcinoma and corresponding normal colonic mucosa. Med Sci Monit. 2008;14:BR219-25 pubmed
    ..In our study we analyzed methylation of CpG islands in the MGMT and p16 genes in sporadic colorectal cancers and normal corresponding colonic mucosa...
  40. Larre Borges A, Borges A, Cuellar F, Puig Butille J, Scarone M, Delgado L, et al. CDKN2A mutations in melanoma families from Uruguay. Br J Dermatol. 2009;161:536-41 pubmed publisher
    ..The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range. ..
  41. Hong J, Resnick M, Behar J, Wang L, Wands J, DeLellis R, et al. Acid-induced p16 hypermethylation contributes to development of esophageal adenocarcinoma via activation of NADPH oxidase NOX5-S. Am J Physiol Gastrointest Liver Physiol. 2010;299:G697-706 pubmed publisher
    Inactivation of tumor suppressor gene p16 may play an important role in the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). Hypermethylation of p16 gene promoter is an important mechanism inactivating p16...
  42. Stott F, Bates S, James M, McConnell B, Starborg M, Brookes S, et al. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2. EMBO J. 1998;17:5001-14 pubmed
    ..The product of the alpha transcript, p16(INK4a), is a recognized tumour suppressor that induces a G1 cell cycle arrest by inhibiting the phosphorylation of the ..
  43. Schulmann K, Sterian A, Berki A, Yin J, Sato F, Xu Y, et al. Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk. Oncogene. 2005;24:4138-48 pubmed
    ..quantitative methylation-specific PCR, we screened 10 genes (HPP1, RUNX3, RIZ1, CRBP1, 3-OST-2, APC, TIMP3, p16, MGMT, p14) for promoter hypermethylation in 77 EAC, 93 BE, and 64 normal esophagus (NE) specimens...
  44. Melk A, Schmidt B, Vongwiwatana A, Rayner D, Halloran P. Increased expression of senescence-associated cell cycle inhibitor p16INK4a in deteriorating renal transplants and diseased native kidney. Am J Transplant. 2005;5:1375-82 pubmed
    ..Somatic cell limitations could contribute to deterioration in aging and disease states. Since expression of p16(INK4a), a cell cycle inhibitor associated with somatic cell senescence in vitro, is induced in aged kidney, we studied ..
  45. Cho Y, Kim T, Lim S, Choi S, Shin H, Lee H, et al. Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population. Diabetologia. 2009;52:253-61 pubmed publisher
    ..Some of the type 2 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans. ..
  46. Le L, Nielsen G, Rosenberg A, Thomas D, Batten J, Deshpande V, et al. Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS ONE. 2011;6:e18846 pubmed publisher
    ..Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/brachyury for proliferation...
  47. Zheng W, Wang H, Xue L, Zhang Z, Tong T. Regulation of cellular senescence and p16(INK4a) expression by Id1 and E47 proteins in human diploid fibroblast. J Biol Chem. 2004;279:31524-32 pubmed
    ..of helix-loop-helix transcriptional regulatory proteins, is implicated in cellular senescence by repressing p16(INK4a) expression, but the mechanisms and cellular effects in human diploid fibroblasts remain unknown...
  48. Wang J, Lee J, Wang L, Liu D, Lu C, Fan Y, et al. Value of p16INK4a and RASSF1A promoter hypermethylation in prognosis of patients with resectable non-small cell lung cancer. Clin Cancer Res. 2004;10:6119-25 pubmed
    The p16INK4a and RASSF1A are tumor suppressor genes frequently inactivated by de novo promoter hypermethylation in non-small cell lung cancer...
  49. Knappskog S, Geisler J, Arnesen T, Lillehaug J, Lønning P. A novel type of deletion in the CDKN2A gene identified in a melanoma-prone family. Genes Chromosomes Cancer. 2006;45:1155-63 pubmed
    ..Here, the defect was identified through detection of a truncated p14(ARF) mRNA and loss of p16(INK4a) mRNA expression from the affected allele...
  50. Chen J, Li D, Wei C, Sen S, Killary A, Amos C, et al. Aurora-A and p16 polymorphisms contribute to an earlier age at diagnosis of pancreatic cancer in Caucasians. Clin Cancer Res. 2007;13:3100-4 pubmed
    Aurora-A and p16 play a major role in cell cycle checkpoint regulation. Both of them are important in the maintenance of centrosome duplication...
  51. Mitomi H, Fukui N, Tanaka N, Kanazawa H, Saito T, Matsuoka T, et al. Aberrant p16((INK4a)) methylation is a frequent event in colorectal cancers: prognostic value and relation to mRNA expression and immunoreactivity. J Cancer Res Clin Oncol. 2010;136:323-31 pubmed publisher
    Aberrant p16((INK4a)) promoter methylation is common in colorectal cancer (CRC), but its clinicopathological significance remains controversial...
  52. Barrett J, Iles M, Harland M, Taylor J, Aitken J, Andresen P, et al. Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet. 2011;43:1108-13 pubmed publisher
    ..6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series. ..
  53. Pollice A, Sepe M, Villella V, Tolino F, Vivo M, Calabro V, et al. TBP-1 protects the human oncosuppressor p14ARF from proteasomal degradation. Oncogene. 2007;26:5154-62 pubmed
    ..The mechanisms that regulate alternative reading frame (ARF) turnover have been obscure for long time, being ARF a relatively stable protein...
  54. Kibel A, Jin C, Klim A, Luly J, A Roehl K, Wu W, et al. Association between polymorphisms in cell cycle genes and advanced prostate carcinoma. Prostate. 2008;68:1179-86 pubmed publisher
    ..61: 95% CI=1.05-6.46). These results suggest that in a European-American population, SNPs within cell cycle genes are promising markers for aggressive PCa. Larger studies will be needed to confirm these findings. ..
  55. Schrage Y, Lam S, Jochemsen A, Cleton Jansen A, Taminiau A, Hogendoorn P, et al. Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro. J Cell Mol Med. 2009;13:2843-52 pubmed publisher
    ..The aim of this study is to investigate genes involved in cell cycle control: CDK4, CDKN2A/p16, cyclin D1, p21, p53, MDM2 and c-MYC, which may point towards new therapeutic strategies...
  56. Chen Z, Lin Y, Barbieri E, Burlingame S, Hicks J, Ludwig A, et al. Mdm2 deficiency suppresses MYCN-Driven neuroblastoma tumorigenesis in vivo. Neoplasia. 2009;11:753-62 pubmed
    ..of the Mdm2/p53 pathway reveals remarkable p53 stabilization counter-balanced by epigenetic silencing of the p19(Arf) gene in the Mdm2 haploinsufficient tumors...
  57. Romagosa C, Simonetti S, López Vicente L, Mazo A, Lleonart M, Castellvi J, et al. p16(Ink4a) overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors. Oncogene. 2011;30:2087-97 pubmed publisher
    p16(Ink4a) is a protein involved in regulation of the cell cycle. Currently, p16(Ink4a) is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors...
  58. Debniak T, Scott R, Masojć B, Serrano Fernandez P, Huzarski T, Byrski T, et al. MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk. Int J Cancer. 2006;119:2597-602 pubmed
    ..The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T. ..
  59. Amente S, Gargano B, Diolaiti D, Della Valle G, Lania L, Majello B. p14ARF interacts with N-Myc and inhibits its transcriptional activity. FEBS Lett. 2007;581:821-5 pubmed
    In this study, we report that the human p14(ARF) associates in vivo with the N-Myc and inhibits N-Myc mediated transcriptional activation...
  60. Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638-45 pubmed publisher
    ..1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. ..
  61. Kamb A, Shattuck Eidens D, Eeles R, Liu Q, Gruis N, Ding W, et al. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet. 1994;8:23-6 pubmed
    ..MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1...
  62. He L, Fan C, Ning X, Feng X, Liu Y, Chen B, et al. Interaction of p14ARF with Brca1 in cancer cell lines and primary breast cancer. Cell Biol Int. 2008;32:1302-9 pubmed publisher
    We report an association between p14ARF and Brca1 in which both proteins co-immunoprecipitate (co-IP) in DU145 cells. The N-terminal 64 residues of p14ARF encoded by exon 1beta are sufficient for this association...
  63. Al Khalaf H, Colak D, Al Saif M, Al Bakheet A, Hendrayani S, Al Yousef N, et al. p16( INK4a) positively regulates cyclin D1 and E2F1 through negative control of AUF1. PLoS ONE. 2011;6:e21111 pubmed publisher
    The cyclin-D/CDK4,6/p16(INK4a)/pRB/E2F pathway, a key regulator of the critical G1 to S phase transition of the cell cycle, is universally disrupted in human cancer...
  64. Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch F. Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement. Cancer Res. 2012;72:4993-5003 pubmed publisher
    ..patterns typical for cervical carcinomas (CxCaRNA(+)), and the HPV-targeted tumor suppressor protein p16(INK4a) as markers for HPV infection...
  65. Grarup N, Rose C, Andersson E, Andersen G, Nielsen A, Albrechtsen A, et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes. 2007;56:3105-11 pubmed publisher
  66. Kriegl L, Neumann J, Vieth M, Greten F, Reu S, Jung A, et al. Up and downregulation of p16(Ink4a) expression in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer. Mod Pathol. 2011;24:1015-22 pubmed publisher
    P16(Ink4a) is an important factor in carcinogenesis and its expression can be linked to oncogene-induced senescence...
  67. Rebouissou S, Hérault A, Letouze E, Neuzillet Y, Laplanche A, Ofualuka K, et al. CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma. J Pathol. 2012;227:315-24 pubmed publisher
  68. Sanchez Aguilera A, Sanchez Beato M, Garcia J, Prieto I, Pollan M, Piris M. p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways. Blood. 2002;99:1411-8 pubmed
    p14(ARF), the alternative product from the human INK4a/ARF locus, antagonizes Hdm2 and mediates p53 activation in response to oncogenic stimuli...
  69. Gallagher S, Kefford R, Rizos H. Enforced expression of p14ARF induces p53-dependent cell cycle arrest but not apoptosis. Cell Cycle. 2005;4:465-72 pubmed
    Expression of the p14ARF tumour suppressor is induced by hyperproliferative signals produced by RAS, MYC and other oncogenes...
  70. Kwong R, Kalish L, Nguyen T, Kench J, Bova R, Cole I, et al. p14ARF protein expression is a predictor of both relapse and survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res. 2005;11:4107-16 pubmed
    The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16(INK4A) and p14(ARF)...
  71. Scott L, Mohlke K, Bonnycastle L, Willer C, Li Y, Duren W, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007;316:1341-5 pubmed
    ..This brings the number of T2D loci now confidently identified to at least 10. ..
  72. Ito S, Ohga T, Saeki H, Watanabe M, Kakeji Y, Morita M, et al. Promoter hypermethylation and quantitative expression analysis of CDKN2A (p14ARF and p16INK4a) gene in esophageal squamous cell carcinoma. Anticancer Res. 2007;27:3345-53 pubmed
    Abnormal hypermethylation of the CDKN2A (p14ARF and p16INK4a) gene can lead to repression of gene expression and contribute to carcinogenesis and tumor progression...
  73. Liu Y, Sanoff H, Cho H, Burd C, Torrice C, Ibrahim J, et al. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell. 2009;8:439-48 pubmed publisher
    Expression of the p16(INK4a) tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments...
  74. Wu X, Gao H, Ke W, Hager M, Xiao S, Freeman M, et al. VentX trans-activates p53 and p16ink4a to regulate cellular senescence. J Biol Chem. 2011;286:12693-701 pubmed publisher
    ..Here, we show that VentX is a direct transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways...
  75. Cánepa E, Scassa M, Ceruti J, Marazita M, Carcagno A, Sirkin P, et al. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life. 2007;59:419-26 pubmed
    ..The members of INK4 family, comprising p16(INK4a), p15(INK4b), p18(INK4c), and p19(INK4d), block the progression of the cell cycle by binding to either Cdk4 or ..
  76. Novara F, Beri S, Bernardo M, Bellazzi R, Malovini A, Ciccone R, et al. Different molecular mechanisms causing 9p21 deletions in acute lymphoblastic leukemia of childhood. Hum Genet. 2009;126:511-20 pubmed publisher
    ..Among the six cases with heterozygous 9p deletions, we found that the remaining CDKN2A and CDKN2B alleles were hypermethylated at CpG islands. ..
  77. Hu C, Zhang R, Wang C, Wang J, Ma X, Lu J, et al. PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population. PLoS ONE. 2009;4:e7643 pubmed publisher
    ..0006). The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively. ..
  78. 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
    b>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 ..
  79. Dong Y, Wang J, Dong F, Wang X, Zhang Y. The correlations between alteration of p16 gene and clinicopathological factors and prognosis in squamous cell carcinomas of the buccal mucosa. J Oral Pathol Med. 2012;41:463-9 pubmed publisher
    To evaluate relationships between the alteration of p16 gene and the clinical status and prognosis of the patients with squamous cell carcinoma of the buccal mucosa. Thirty buccal cancers were included in the analysis...
  80. Kuo M, den Besten W, Bertwistle D, Roussel M, Sherr C. N-terminal polyubiquitination and degradation of the Arf tumor suppressor. Genes Dev. 2004;18:1862-74 pubmed
    Unknown mechanisms govern degradation of the p19Arf tumor suppressor, an activator of p53 and inhibitor of ribosomal RNA processing...
  81. Kia S, Gorski M, Giannakopoulos S, Verrijzer C. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol Cell Biol. 2008;28:3457-64 pubmed publisher
    Stable silencing of the INK4b-ARF-INK4a tumor suppressor locus occurs in a variety of human cancers, including malignant rhabdoid tumors (MRTs)...
  82. Anschau F, Schmitt V, Lambert A, Gonçalves M, Machado D. Transition of cervical carcinoma in situ to invasive cancer: role of p16 INK4a expression in progression and in recurrence. Exp Mol Pathol. 2009;86:46-50 pubmed publisher
    To investigate the expression of p16(INK4a) in cervical carcinoma and its relation to the transition of carcinoma in situ to invasive carcinoma, and its role in recurrence of cervical lesions as well, a series of 90 patients with ..
  83. Huang M, Li H, Nie X, Wu X, Jiang X. An analysis on the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions. Diagn Cytopathol. 2010;38:573-8 pubmed publisher
    ..The aims of this study were to detect the expression of HPV L1 capsid protein and p16(INK4a) in cervical lesions and to investigate the combination expression of HPV L1 capsid protein and p16(INK4a) in ..
  84. Chen D, Shan J, Zhu W, Qin J, Gu W. Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses. Nature. 2010;464:624-7 pubmed publisher
    The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress...
  85. Clark P, Llanos S, Peters G. Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2. Oncogene. 2002;21:4498-507 pubmed
    The small basic protein p14ARF, encoded by one of the alternative transcripts from the human INK4A/ARF locus, interferes with MDM2-mediated ubiquitination of the p53 tumour suppressor protein...
  86. Goldstein A, Chan M, Harland M, Gillanders E, Hayward N, Avril M, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66:9818-28 pubmed
    ..in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal ..
  87. Mroz E, Baird A, Michaud W, Rocco J. COOH-terminal binding protein regulates expression of the p16INK4A tumor suppressor and senescence in primary human cells. Cancer Res. 2008;68:6049-53 pubmed publisher
    ..CtBP had little influence on the expression of the alternate product of the CDKN2A tumor-suppressor gene, p14(ARF)...
  88. Lessard F, Morin F, Ivanchuk S, Langlois F, Stefanovsky V, Rutka J, et al. The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I. Mol Cell. 2010;38:539-50 pubmed publisher
    The p14/p19(ARF) (ARF) product of the CDKN2A gene displays tumor suppressor activity both in the presence and absence of p53/TP53...
  89. Lewis J, Thorstad W, Chernock R, Haughey B, Yip J, Zhang Q, et al. p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34:1088-96 pubmed publisher
    ..Many recommend use of both p16 immunohistochemistry and HPV in situ hybridization (ISH)...