CDKN2A - cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
Entrez Gene Name: cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
Entrez GeneID: Human(1029)
, Mouse(12578), Rat(25163)
, Mouse(12578), Rat(25163) Synonyms: ARF, ARF-INK4a, CDK4I, CDKN2, CDKN2A, CMM2, CYCLIN-DEPENDENT KINASE INHIBITOR 2A, INK4, INK4A, INK4a-ARF, Ink4a/Arf, MLM, MTS1, p14, p14/ARF, p14ARF, P16, p16(INK4a), p16Cdkn2a, p16INK4, P16INK4A, p19, p19ARF, PCTR1, TP16
Gene Summary
- Human (1029): 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, MDM1, 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]
- Rat (25163): tumor suppressor that inhibits CDK4; inactivation or loss is associated with cellular transformation; may be involved in CNS degeneration following injury [RGD]
Molecular Functions | Biological Process | Cellular Components | Protein Domains | Subcellular Locations | Pathways | Literature References | IPA Extras
Cell Regulation
Biological Process
activation of caspase activity, aging, apoptosis, apoptotic mitochondrial changes, cell aging, cell cycle, cell cycle arrest, cell cycle checkpoint, DNA fragmentation involved in apoptosis, epidermis development, G1/S transition of mitotic cell cycle, induction of apoptosis, negative regulation of B cell proliferation, negative regulation of cell cycle, 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 immature T cell proliferation in the thymus, negative regulation of NF-kappaB transcription factor activity, negative regulation of phosphorylation, negative regulation of protein kinase activity, negative regulation of ubiquitin-protein ligase activity, positive regulation of DNA damage response, signal transduction by p53 class mediator, regulation of cyclin-dependent protein kinase activity, regulation of G2/M transition of mitotic cell cycle, regulation of gene expression, regulation of nucleocytoplasmic transport, regulation of protein stability, regulation of transcription, DNA-dependent, response to drug, response to organic cyclic substance, response to organic nitrogen, response to organic substance, rRNA processing, rRNA transcription, senescence, somatic stem cell division, transcription
Literature References
- 18519632Mullighan CG, Williams RT, Downing JR, Sherr CJ. Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL.Genes Dev 2008 Jun 01;22(11):1411-5
- 17344414Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Mönch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells.Genes Dev 2007 Mar 01;21(5):525-30
- 16037818Silva RL, Thornton JD, Martin AC, Rehg JE, Bertwistle D, Zindy F, Skapek SX. Arf-dependent regulation of Pdgf signaling in perivascular cells in the developing mouse eye.EMBO J 2005 Aug 03;24(15):2803-14 View 5100 categorized literature findings and their references in IPA
Molecular Functions
cyclin-dependent protein kinase inhibitor activity, DNA binding, kinase activity, NF-kappaB binding, protein binding, protein kinase binding, transcription factor activity, ubiquitin-protein ligase inhibitor activity
- Cell Cycle: G1/S Checkpoint Regulation
- Chronic Myeloid Leukemia Signaling
- Bladder Cancer Signaling
- Melanoma Signaling
- Myc Mediated Apoptosis Signaling
- Cell Cycle: G2/M DNA Damage Checkpoint Regulation
- p53 Signaling
- Wnt/β-catenin Signaling
- Non-Small Cell Lung Cancer Signaling
- Molecular Mechanisms of Cancer
- HGF Signaling
- Glioma Signaling
- Aryl Hydrocarbon Receptor Signaling
- Pancreatic Adenocarcinoma Signaling
Protein Domains
ankyrin repeat, cyclin-dependent protein kinase inhibitor, Mdm2 protein binding domain, N-terminal domain, nucleolar targeting motif, protein binding, protein kinase binding, transcription factor, transcription regulator
Subcellular Locations
chromatin fraction, cytoplasm, cytosol, nuclear bodies, nuclear matrix fraction, nuclear speckles, nucleoli, nucleolus derived foci, nucleoplasm, nucleus, plasma membrane, prenucleolar bodies
