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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. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; Nucleolus; Tumor suppressor
Chromosomal Location of Human Ortholog: 9p21.3
Cellular Component: cytoplasm; cytosol; nucleus
Molecular Function: cyclin-dependent protein kinase inhibitor activity; NF-kappaB binding; protein binding; protein kinase binding; RNA binding
Biological Process: cell cycle arrest; G1/S transition of mitotic cell cycle; inhibition of NF-kappaB transcription factor; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell-matrix adhesion; negative regulation of cyclin-dependent protein kinase activity; negative regulation of phosphorylation; negative regulation of transcription, DNA-dependent; Ras protein signal transduction
Disease: Melanoma, Cutaneous Malignant, Susceptibility To, 2; Melanoma-astrocytoma Syndrome; Melanoma-pancreatic Cancer Syndrome
Reference #:  P42771 (UniProtKB)
Alt. Names/Synonyms: ARF; CD2A1; CDK4 inhibitor p16-INK4; CDK4I; CDKN2; CDKN2A; cell cycle negative regulator beta; CMM2; Cyclin-dependent kinase 4 inhibitor A; cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4); cyclin-dependent kinase inhibitor 2A, isoform 4; Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3; cyclin-dependent kinase inhibitor p16; INK4; INK4a; MLM; MTS-1; MTS1; Multiple tumor suppressor 1; p14; p14ARF; p16; p16-INK4; p16-INK4a; p16INK4; p16INK4A; p19; p19Arf; TP16
Gene Symbols: CDKN2A
Molecular weight: 16,533 Da
Basal Isoelectric point: 5.52  Predict pI for various phosphorylation states
CST Pathways:  G1/S Checkpoint
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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