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p14ARF (human)

Overview p14ARF 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. Cellular Component: nucleoplasm; nuclear body; protein complex; cytoplasm; nucleolus; nucleus; cytosol Molecular Function: cyclin-dependent protein kinase inhibitor activity; NF-kappaB binding; protein binding; DNA binding; p53 binding; ubiquitin-protein ligase inhibitor activity; transcription factor activity; protein kinase binding; transcription factor binding Biological Process: epidermis development; protein polyubiquitination; somatic stem cell maintenance; positive regulation of transcription, DNA-dependent; positive regulation of apoptosis involved in mammary gland involution; regulation of protein stability; negative regulation of B cell proliferation; regulation of protein export from nucleus; negative regulation of cell proliferation; apoptotic mitochondrial changes; regulation of G2/M transition of mitotic cell cycle; somatic stem cell division; DNA fragmentation during apoptosis; G1 phase of mitotic cell cycle; cell cycle arrest; negative regulation of immature T cell proliferation in the thymus; caspase activation; protein stabilization; protein destabilization; transcription, DNA-dependent; negative regulation of cyclin-dependent protein kinase activity; negative regulation of cell-matrix adhesion; negative regulation of mammary gland epithelial cell proliferation; rRNA transcription; positive regulation of protein sumoylation; inhibition of NF-kappaB transcription factor; regulation of nucleocytoplasmic transport; Ras protein signal transduction; induction of apoptosis; negative regulation of ubiquitin-protein ligase activity; negative regulation of phosphorylation; negative regulation of protein kinase activity; positive regulation of transcription from RNA polymerase II promoter; mitotic cell cycle; positive regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of cell growth; negative regulation of transcription, DNA-dependent; cell cycle checkpoint; rRNA processing; G1/S transition of mitotic cell cycle Reference #:  Q8N726 (UniProtKB) Alt. Names/Synonyms: ARF; CD2A2; 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: 13,903 Da Basal Isoelectric point: 12.41  Predict pI for various phosphorylation states CST Pathways:  Cell Cycle: G2/M DNA Damage Checkpoint Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below p14ARF

STRING  |  Scansite  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  DISEASE 151623 155601 155755 600160 606719  |  Source  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	Modification Sites and Domains

	Modification Sites in Parent Protein, Orthologs, and Isoforms

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
1	0		T8-p	MVRRFLVtLRIRRAC

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