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: Tumor suppressor; Nucleolus; Cell cycle regulation
Cellular Component: cytoplasm; granular component; mitochondrion; nuclear body; nucleolus; nucleoplasm; nucleus; protein complex
Molecular Function: cyclin-dependent protein kinase inhibitor activity; DNA binding; NF-kappaB binding; p53 binding; protein binding; protein kinase binding; protein N-terminus binding; transcription factor activity; transcription factor binding; ubiquitin-protein ligase inhibitor activity
Biological Process: aging; apoptosis; apoptotic mitochondrial changes; caspase activation; cell aging; cell cycle; cell cycle arrest; epidermis development; G1/S transition of mitotic cell cycle; glucose homeostasis; inhibition of NF-kappaB transcription factor; mitochondrial depolarization; mitochondrion degradation; 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 mammary gland epithelial cell proliferation; negative regulation of phosphorylation; negative regulation of protein binding; negative regulation of protein kinase activity; negative regulation of transcription, DNA-dependent; negative regulation of ubiquitin-protein ligase activity; positive regulation of apoptosis; positive regulation of apoptosis involved in mammary gland involution; positive regulation of DNA damage response, signal transduction by p53 class mediator; positive regulation of protein sumoylation; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; protein destabilization; protein polyubiquitination; protein stabilization; 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 export from nucleus; regulation of protein stability; regulation of transcription, DNA-dependent; response to drug; response to organic cyclic substance; response to organic nitrogen; rRNA processing; rRNA transcription; somatic stem cell division; somatic stem cell maintenance; transcription, DNA-dependent
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