p16INK4a Proteins

Protein Information

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, the E3 ubiquitin-protein ligase MDM2, 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.

Synonyms

Alternative reading frame; Arf; ARF-INK4a; CDK4 inhibitor p16 INK4; CDK4 inhibitor p16-INK4; CDK4I; CDKN2; Cdkn2a; cdkn2a {ECO:0000312; cell cycle inhibitor; cell cycle negative regulator beta; cell cycle regulator; CMM2; Cyclin dependent kinase 4 inhibitor A; cyclin dependent kinase inhibitor 2A; Cyclin dependent kinase inhibitor 2A (p16, inhibits CDK4); 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 (p16, inhibits CDK4); cyclin-dependent kinase inhibitor 2a p16Ink4a; cyclin-dependent kinase inhibitor 2a p19Arf; cyclin-dependent kinase inhibitor 2A, isoform 1; cyclin-dependent kinase inhibitor 2A, isoform 2; cyclin-dependent kinase inhibitor 2A, isoform 3; cyclin-dependent kinase inhibitor 2A, isoforms 1/2; cyclin-dependent kinase inhibitor protein; EMBL:AAL76336.1, ECO:0000312; EMBL:AAL76338.1, ECO:0000312; HGNC:1787; inhibits CDK4; INK4; INK4A; Ink4a/Arf; INK4a-ARF; isoforms 1/2/3; Melanoma p16 inhibits CDK4; mitochondrial smARF; MLM; MTS1; MTS-1; Multiple tumor suppressor 1; P14; P14 P16; P14ARF; p16; p16(INK4a); p16Cdkn2a; P16INK4; p16-INK4; p16INK4a; p16-INK4a; P19; P19 TP16; p19; P19ARF; Pctr1; RGD:2323}; TP16; Tumor suppressor ARF