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Official Full Name: cyclin dependent kinase inhibitor 2A
Also known as: ARF; MLM; P14; P16; P19; CMM2; INK4; MTS1; TP16; CDK4I; CDKN2; INK4A; MTS-1; P14ARF; P19ARF; P16INK4; P16INK4A; P16-INK4A
This gene produces several transcript variants that differ in the first exon. At least three alternatively spliced variants have been reported to encode distinct proteins, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternative first exon located 20 kb upstream of the remainder of the gene; this transcript contains an alternative open reading frame (ARF) that specifies a protein that is structurally unrelated to the product of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester the E3 ubiquitin protein ligase MDM2, a protein responsible for the degradation of p53. Despite structural and functional differences, CDK inhibitor isoforms and the ARF product encoded by this gene share a common function in cell cycle G1 control through the regulation of CDK4 and p53 in cell cycle G1 progression. This gene is often mutated or deleted in a variety of tumors and is an important tumor suppressor gene.