Cyclin Dependent Kinase Inhibitor 2a (CDKN2A) Antibody – Rabbit Polyclonal

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. [provided by RefSeq, Sep 2012]

p16-INK4A: a cell-cycle regulatory protein that interacts with CDK4 and CDK6, inhibiting their ability to interact with cyclins D. Inhibits the phosphorylation of the retinoblastoma protein by CDK4 or CDK6, and entry into the S phase of the cell cycle. The p16INK4A and p14ARF proteins are encoded by CDKN2A, a known tumour suppressor gene in multiple cancers. CDKN2A is inactivated in 72% of cases of lung squamous cell carcinoma: 21% by epigenetic silencing by methylation, 18% inactivating mutation, 4% by exon 1b skipping, and 29% by homozygous deletion. Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome, Li-Fraumeni syndrome, and the melanoma-astrocytoma syndrome. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma. Four alternatively spliced p16 isoforms have been reported. Two alternatively spliced isoforms of ARF have been reported.

Protein type: Cell cycle regulation; Nucleolus; Tumor suppressor

Chromosomal Location of Human Ortholog: 9p21.3

Cellular Component: cytoplasm; cytosol; nucleus; senescence-associated heterochromatin focus

Molecular Function: cyclin-dependent protein serine/threonine kinase inhibitor activity; NF-kappaB binding; protein binding; protein kinase binding; RNA binding

Biological Process: cell cycle arrest; cellular senescence; G1/S transition of mitotic cell cycle; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell-matrix adhesion; negative regulation of cyclin-dependent protein serine/threonine kinase activity; negative regulation of NF-kappaB transcription factor activity; negative regulation of phosphorylation; negative regulation of transcription, DNA-dependent; positive regulation of cellular senescence; positive regulation of macrophage apoptotic process; positive regulation of smooth muscle cell apoptotic process; Ras protein signal transduction; replicative senescence; senescence-associated heterochromatin focus assembly

Disease: Melanoma, Cutaneous Malignant, Susceptibility To, 2; Melanoma-astrocytoma Syndrome; Melanoma-pancreatic Cancer Syndrome