Cyclin Dependent Kinase Inhibitor 2A (CDKN2A)

P16; ARF; CDK4I; CMM2; INK4; INK4a; MLM; MTS1; TP16; P14; P14ARF; P16INK4a; P19; Melanoma P16; Cyclin-dependent kinase 4 inhibitor A; Multiple tumor suppressor 1

SPN	W018
HGNC	1787
MGI	104738
PubMed	18559569
RGD	1578733
UniProt	P42771
Wiki	CDKN2A

• CDKN2A, is a tumor suppressor protein, which in humans is encoded by the CDKN2A gene.P16 plays an important role in regulating the cell cycle, and mutations in p16 increase the risk of developing a variety of cancers, notably melanoma.

• This gene generates several transcript variants which differ in their first exons. At least three alternatively-spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants.

Reference

"A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4."
Nature 366:704-707(1993) [PubMed] [Europe PMC] [Abstract]

"Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus."
Oncogene 18:3810-3820(1999) [PubMed] [Europe PMC] [Abstract]

"Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemia."
J. Biol. Chem. 277:46289-46297(2002) [PubMed] [Europe PMC] [Abstract]

"Human p16gamma, a novel transcriptional variant of p16(INK4A), coexpresses with p16(INK4A) in cancer cells and inhibits cell-cycle progression."
Oncogene 26:7017-7027(2007) [PubMed] [Europe PMC] [Abstract]

"DNA sequence and analysis of human chromosome 9."
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]

"Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence."
Mol. Cell. Biol. 16:859-867(1996) [PubMed] [Europe PMC] [Abstract]

"Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers."
Nature 368:753-756(1994) [PubMed] [Europe PMC] [Abstract]

"A cell cycle regulator potentially involved in genesis of many tumor types."
Science 264:436-440(1994) [PubMed] [Europe PMC] [Abstract]

"Mutations and altered expression of p16INK4 in human cancer."
Proc. Natl. Acad. Sci. U.S.A. 91:11045-11049(1994) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of p16INK4A correlates with Cdk4 association."
J. Biol. Chem. 278:6619-6622(2003) [PubMed] [Europe PMC] [Abstract]

"Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'."
Mol. Cell. Biol. 26:5070-5085(2006) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a."
Biochem. Biophys. Res. Commun. 361:287-293(2007) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a."
Nature 395:237-243(1998) [PubMed] [Europe PMC] [Abstract]

"Tumor suppressor INK4: comparisons of conformational properties between p16(INK4A) and p18(INK4C)."
J. Mol. Biol. 294:201-211(1999) [PubMed] [Europe PMC] [Abstract]

"Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data."
Protein Sci. 9:1120-1128(2000) [PubMed] [Europe PMC] [Abstract]

"CDKN2 mutations in melanoma."
Cancer Surv. 26:115-132(1996) [PubMed] [Europe PMC] [Abstract]

"CDKN2A (p16INK4A) somatic and germline mutations."
Hum. Mutat. 7:294-303(1996) [PubMed] [Europe PMC] [Abstract]

"Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas."
Biochem. Biophys. Res. Commun. 202:1426-1430(1994) [PubMed] [Europe PMC] [Abstract]

"Germline p16 mutations in familial melanoma."
Nat. Genet. 8:15-21(1994) [PubMed] [Europe PMC] [Abstract]

"The MTS1 gene is frequently mutated in primary human esophageal tumors."
Oncogene 9:3737-3741(1994) [PubMed] [Europe PMC] [Abstract]

"Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer."
Cancer Res. 55:1448-1451(1995) [PubMed] [Europe PMC] [Abstract]

"Mutations of the CDKN2/p16INK4 gene in Australian melanoma kindreds."
Hum. Mol. Genet. 4:1845-1852(1995) [PubMed] [Europe PMC] [Abstract]

"Mutations associated with familial melanoma impair p16INK4 function."
Nat. Genet. 10:114-116(1995) [PubMed] [Europe PMC] [Abstract]

"Novel germline p16 mutation in familial malignant melanoma in southern Sweden."
Cancer Res. 56:2497-2500(1996) [PubMed] [Europe PMC] [Abstract]

"Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population."
Proc. Natl. Acad. Sci. U.S.A. 93:8541-8545(1996) [PubMed] [Europe PMC] [Abstract]

"Germline mutations of the CDKN2 gene in UK melanoma families."
Hum. Mol. Genet. 6:2061-2067(1997) [PubMed] [Europe PMC] [Abstract]

"Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France."
Hum. Mol. Genet. 7:209-216(1998) [PubMed] [Europe PMC] [Abstract]

Erratum
Hum. Mol. Genet. 7:941-941(1998)

"Five novel somatic CDKN2/p16 mutations identified in melanoma, glioma and carcinoma of the pancreas."
Hum. Mutat. 12:212-212(1998) [PubMed] [Europe PMC] [Abstract]

"Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family."
Cancer Genet. Cytogenet. 113:145-151(1999) [PubMed] [Europe PMC] [Abstract]

"A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families."
Br. J. Cancer 85:527-530(2001) [PubMed] [Europe PMC] [Abstract]

"A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family."
Hum. Mol. Genet. 10:55-62(2001) [PubMed] [Europe PMC] [Abstract]

"Germline mutation of ARF in a melanoma kindred."
Hum. Mol. Genet. 11:1273-1279(2002) [PubMed] [Europe PMC] [Abstract]

"CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia."
J. Med. Genet. 36:490-493(1999) [PubMed] [Europe PMC] [Abstract]

"Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma."
Invest. Ophthalmol. Vis. Sci. 44:458-462(2003) [PubMed] [Europe PMC] [Abstract]

"A novel L94Q mutation in the CDKN2A gene in a melanoma kindred."
Melanoma Res. 13:567-570(2003) [PubMed] [Europe PMC] [Abstract]

"Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients."
Hum. Mutat. 30:564-574(2009) [PubMed] [Europe PMC] [Abstract]