cyclin dependent kinase inhibitor 2A
Last updated 20 Mar 2023
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The CDKN2A gene provides instructions for making several proteins. The most well-studied are the p16(INK4A) and the p14(ARF) proteins. Both function as tumour suppressors, which means they keep cells from growing and dividing too rapidly or in an uncontrolled way. Both proteins are also involved in stopping cell division in older cells (senescence).
Normal function
The CDKN2A gene provides instructions for making several proteins. The most well-studied are the p16(INK4A) and the p14(ARF) proteins. Both function as tumour suppressors, which means they keep cells from growing and dividing too rapidly or in an uncontrolled way. Both proteins are also involved in stopping cell division in older cells (senescence).
The p16(INK4A) protein attaches (binds) to two other proteins called CDK4 and CDK6. These proteins help regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. CDK4 and CDK6 normally stimulate the cell to continue through the cycle and divide. However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. In this way, p16(INK4A) controls cell division. Cells begin to produce p16(INK4A) when they are no longer able to undergo cell division.
The p14(ARF) protein protects a different protein called p53 from being broken down. The p53 protein is an important tumour suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). By protecting p53, p14(ARF) also helps prevent tumour formation. The p14(ARF) and p53 proteins are often made in cells that are unable to undergo cell division.
Conditions referring to this gene or chromosome
Other names
ARF
CDK4 inhibitor p16-INK4
CDK4I
CDKN2
cell cycle negative regulator beta
CMM2
cyclin-dependent kinase 4 inhibitor A
cyclin-dependent kinase inhibitor 2A
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
cyclin-dependent kinase inhibitor 2A isoform p12
cyclin-dependent kinase inhibitor 2A isoform p14ARF
cyclin-dependent kinase inhibitor 2A isoform p16gamma
cyclin-dependent kinase inhibitor 2A isoform p16INK4a
INK4
INK4A
MLM
MTS-1
MTS1
multiple tumour suppressor 1
P14
P14ARF
P16
P16-INK4A
P16INK4
P16INK4A
P19
P19ARF
TP16
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Further reading and references
- cyclin dependent kinase inhibitor 2A; MedlinePlus, National Library of Medicine.
- Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016 Feb 11;530(7589):184-9. doi: 10.1038/nature16932. Epub 2016 Feb 3.
- Canepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, Ogara MF. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life. 2007 Jul;59(7):419-26. doi: 10.1080/15216540701488358.
- Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, Azizi E, Bianchi-Scarra G, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon Albright LA, Demenais F, Elder DE, Ghiorzo P, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Niendorf K, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, de Snoo FA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E; Melanoma Genetics Consortium (GenoMEL). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006 Oct 15;66(20):9818-28. doi: 10.1158/0008-5472.CAN-06-0494.
- He S, Sharpless NE. Senescence in Health and Disease. Cell. 2017 Jun 1;169(6):1000-1011. doi: 10.1016/j.cell.2017.05.015.
- Jeck WR, Siebold AP, Sharpless NE. Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell. 2012 Oct;11(5):727-31. doi: 10.1111/j.1474-9726.2012.00871.x. Epub 2012 Aug 30.
- Lim AM, Do H, Young RJ, Wong SQ, Angel C, Collins M, Takano EA, Corry J, Wiesenfeld D, Kleid S, Sigston E, Lyons B, Fox SB, Rischin D, Dobrovic A, Solomon B. Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome. Int J Cancer. 2014 Aug 15;135(4):887-95. doi: 10.1002/ijc.28727. Epub 2014 Jan 30.
- Loyo M, Li RJ, Bettegowda C, Pickering CR, Frederick MJ, Myers JN, Agrawal N. Lessons learned from next-generation sequencing in head and neck cancer. Head Neck. 2013 Mar;35(3):454-63. doi: 10.1002/hed.23100. Epub 2012 Aug 21.
- Mountzios G, Rampias T, Psyrri A. The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact. Ann Oncol. 2014 Oct;25(10):1889-1900. doi: 10.1093/annonc/mdu143. Epub 2014 Apr 8.
- Potrony M, Puig-Butille JA, Aguilera P, Badenas C, Carrera C, Malvehy J, Puig S. Increased prevalence of lung, breast, and pancreatic cancers in addition to melanoma risk in families bearing the cyclin-dependent kinase inhibitor 2A mutation: implications for genetic counseling. J Am Acad Dermatol. 2014 Nov;71(5):888-95. doi: 10.1016/j.jaad.2014.06.036. Epub 2014 Jul 24.
- Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28.
- Taylor NJ, Mitra N, Goldstein AM, Tucker MA, Avril MF, Azizi E, Bergman W, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon-Albright LA, Cuellar F, Cust AE, Demenais F, Elder DE, Gerdes AM, Ghiorzo P, Grazziotin TC, Hansson J, Harland M, Hayward NK, Hocevar M, Hoiom V, Ingvar C, Landi MT, Landman G, Larre-Borges A, Leachman SA, Mann GJ, Nagore E, Olsson H, Palmer JM, Peric B, Pjanova D, Pritchard A, Puig S, van der Stoep N, Wadt KAW, Whitaker L, Yang XR, Newton Bishop JA, Gruis NA, Kanetsky PA; GenoMEL Study Group. Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families. J Invest Dermatol. 2017 Dec;137(12):2606-2612. doi: 10.1016/j.jid.2017.07.829. Epub 2017 Aug 19.
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