| Name | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) |
| Symbol | CDKN2A |
| Aliases | ARF; MLM; P16; p14; p16; p19; CMM2; INK4; MTS1; TP16; CDK4I; CDKN2; INK4a; p14ARF; p16INK4; CDK4 inhibitor p16-INK4; multiple tumor suppressor 1; cell cycle negative regulator beta; cyclin-dependent kinase inhibitor p16; cyclin-dependent kinase inhibitor p12, p16INK4a alternatively spliced form |
| Gene Product | - alternative reading frame p14
- cyclin-dependent kinase inhibitor 2A isoform 1
- cyclin-dependent kinase inhibitor 2A isoform 3
|
| Category | |
| UniGene |
Hs.421349
|
| Reference Sequence |
|
| OMIM and SNP |
|
| Locus |
|
| Summary | 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. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. |
| Gene Ontology | |
| Expression | | EST (209 ESTs, 82 libraries) |
| Tissue | Breadth ? |
CPM ? |
| blood |  | | | bone | | | | brain | | | | cartilage | | | | cervix | | | | colon | | | | eye | | | | germ cell | | | | kidney |  | | | liver | | | | lung | | | | lymph node | | | | mammary gland | | | | muscle | | | | nervous | | | | oral cavity | | | | ovary | | | | pancreas | | | | placenta | | | | prostate | | | | skin | | | | stomach | | | | testis | | | | uncharacterized tissue | | | | uterus | | |
|
| SAGE (4681195 tags, 93 libraries) |
| Tissue | Breadth ? |
CPM ? |
| brain | | | | cervix | | | | colon | | | | eye | | | | foreskin | | | | kidney | | | | mammary gland | | | | mesothelial tissue | | | | ovary | | | | pancreas | | | | prostate | | | | skin | | | | stomach | | | | uncharacterized tissue | | | | vascular | | |
|
|
| Evidence | CpG Methylation in Kidney Neoplasms
- Kawada Y, Nakamura M, Ishida E, Shimada K, Oosterwijk E, Uemura H, Hirao Y, Chul KS, Konishi N, Kawada Y, Nakamura M, Ishida E, Shimada K, Oosterwijk E, Uemura H, Hirao Y, Chul KS, Konishi N Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas. Jpn J Cancer Res 2001 Dec;92(12):1293-9.
- Esteller M, Cordon-Cardo C, Corn PG, Meltzer SJ, Pohar KS, Watkins DN, Capella G, Peinado MA, Matias-Guiu X, Prat J, Baylin SB, Herman JG, Esteller M, Cordon-Cardo C, Corn PG, Meltzer SJ, Pohar KS, Watkins DN, Capella G, Peinado MA, Matias-Guiu X, Prat J, Baylin SB, Herman JG, Esteller M, Cordon-Cardo C, Corn PG, Meltzer SJ, Pohar KS, Watkins DN, Capella G, Peinado MA, Matias-Guiu X, Prat J, Baylin SB, Herman JG p14ARF silencing by promoter hypermethylation mediates abnormalintracellular localization of MDM2. Cancer Res 2001 Apr 1;61(7):2816-21.
- Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S, Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S, Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S High incidence of allelic loss on chromosome 5 and inactivation ofp15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renalcell carcinoma of rats. Oncogene 1999 Jun 24;18(25):3793-7.
- Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB, Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB Inactivation of the CDKN2/p16/MTS1 gene is frequently associated withaberrant DNA methylation in all common human cancers. Cancer Res 1995 Oct 15;55(20):4525-30.
Deletion in Kidney Neoplasms
- Kawada Y, Nakamura M, Ishida E, Shimada K, Oosterwijk E, Uemura H, Hirao Y, Chul KS, Konishi N, Kawada Y, Nakamura M, Ishida E, Shimada K, Oosterwijk E, Uemura H, Hirao Y, Chul KS, Konishi N Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas. Jpn J Cancer Res 2001 Dec;92(12):1293-9.
- Kinoshita H, Yamada H, Ogawa O, Kakehi Y, Osaka M, Nakamura E, Mishina M, Habuchi T, Takahashi R, Sugiyama T, et al. Contribution of chromosome 9p21-22 deletion to the progression of humanrenal cell carcinoma. Jpn J Cancer Res 1995 Sep;86(9):795-9.
Other key publications related to this gene
|
