p14ARF Antibodies

Target Information

a tumor suppressor and regulator of cell cycle arrest at G2/M. The ARF isoform functions as a stabilizer of the tumor suppressor protein p53 by sequestering MDM2, a protein responsible for the degradation of p53. Blocks the nucleocytoplasmic shuttling of MDM2 by sequestering it in the nucleolus, relieving p53 from degradation, and enabling p53-dependent transactivation and apoptosis. At least three alternatively spliced variants encoding distinct 'p14' proteins have been reported. Two encode structurally related isoforms that induce G2 arrest and apoptosis in a p53-independent manner by preventing the activation of CDC2 by cyclin B1. 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. 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 Cdc2 and p53 in cell cycle G1 progression, share a common functionality in cell cycle control. Does not interact with cyclins, CDK2, CDK4, CDK5 or CDK6. Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1, TOP1 and UBE2I. Interacts with TBRG1 and COMMD1. Interacts with CARF and E4F1. The p14ARF and p16INK4A 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. Note: This description may include information from UniProtKB.

Alternate Names

Alternative reading frame; ARF; ARF-; ARF-INK4a; CD2A2; CDK4 inhibitor p16-INK4; CDK4I; CDKN2; CDKN2A; Cdkn2a; cell cycle negative regulator beta; CMM2; cyclin dependent kinase inhibitor 2A; 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, isoform 3; Cyclin-dependent kinase inhibitor 2A, isoform 4; cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3; cyclin-dependent kinase inhibitor p16; cyclin-dependent kinase inhibitor protein; INK4; INK4a; INK4a-ARF; Ink4a/Arf; mitochondrial smARF; MLM; MTS; MTS-1; MTS1; multiple tumor suppressor 1; p14; p14ARF; p16; p16-INK4; p16-INK4a; p16-INK4A iso3; p16-INK4A iso5; p16(INK4a); p16I; p16INK4; p16INK4a; p19; p19; p19ARF; Pct; Pctr1; TP16; Tumor suppressor ARF