CDKN1B KIP1

CDKN1B ;
KIP1 ;
Cyclin-dependent kinase inhibitor 1B ;
Cyclin-dependent kinase inhibitor p27 ;
p27Kip1

disease:Defects in CDKN1B are the cause of multiple endocrine neoplasia type 4 (MEN4) [MIM:610755]. Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2. ,domain:A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity. ,function:Important regulator of cell cycle progrssion. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Positive regulator of cyclin D-dependent kinases such as CDK4. Regulated by phosphorylation and degradation events. ,induction:Maximal levels in quiescence cells and early G (1) . Levels decrease after mitogen stimulation as cells progress toward S-phase. ,miscellaneous:Decreased levels of p27Kip1 , mainly due to proteosomal degradation , are found in various epithelial tumors originating from lung , breast , colon , ovary , esophagus , thyroid and prostate. ,PTM:Phosphorylated; phosphorylation occurs on serine , threonine and tyrosine residues. Phosphorylation on Ser-10 is the major site of phosphorylation in resting cells , takes place at the G (0) -G (1) phase and leads to protein stability. Phosphorylation on other sites is greatly enhanced by mitogens , growth factors , cMYC and in certain cancer cell lines. The phosphorylated form found in the cytoplasm is inactivate. Phosphorylation on Thr-198 is required for interaction with 14-3-3 proteins. Phosphorylation on Thr-187 , by CDK2 leads to protein ubiquitination and proteasomal degradation. Tyrosine phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can be suppressed by LY294002 , an inhibitor of the catalytic subunit of PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding CDK2 , but is required for binding CDK4. Dephosphorylated on tyrosine residues by G-CSF. ,PTM:Ubiquitinated; in the cytoplasm by the KPC1/KPC2 complex and , in the nucleus , by SCF/SKP2. The latter requires prior phosphorylation on Thr-187. ,similarity:Belongs to the CDI family. ,subcellular location:Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-198 , binds 14-3-3 , translocates to the cytoplasm and promotes cell cycle progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in translocation to the cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus on phosphorylation of Tyr-88 and Tyr-89. ,subunit:Interacts with NUP50; the interaction leads to nuclear import and degradation of phosphorylated p27kip1. Interacts with COPS5 , subunit of the COP9 signalosome complex; the interaction leads to p27KIP degradation. Interacts with SPDYA in the SPDYA/CDK2/p27kip1 complex. Interacts (Thr-198 phosphorylated-form) with 14-3-3 proteins , binds strongly YWHAQ , weakly YWHAE and YWHAH , but not YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to the cytoplasm. Interacts with AKT1 , LYN and UHMK1; the interactions lead to cytoplasmic mislocation , phosphorylation of p27kip1 and inhibition of cell cycle arrest. Interacts (unphosphorylated form) with CDK2. Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the interaction induces nuclear translocation. Interacts with GRB2. ,tissue specificity:Expressed in all tissues tested. Highest levels in skeletal muscle , lowest in liver and kidney. ,

regulation of cyclin-dependent protein kinase activity , G1/S transition of mitotic cell cycle , mitotic cell cycle , regulation of cell growth , regulation of transcription , DNA-dependent , negative regulation of protein kinase activity , ion transport ,cation transport , potassium ion transport , induction of apoptosis , cell cycle , cell cycle arrest , sensory organ development , sensory perception , sensory perception of sound , cell death , positive regulation of cell proliferation ,negative regulation of cell proliferation , regulation of cell size , negative regulation of biosynthetic process , negative regulation of macromolecule biosynthetic process , negative regulation of phosphorus metabolic process , negative regulation of macromolecule metabolic process , negative regulation of gene expression , positive regulation of organelle organization , regulation of cell death , positive regulation of cell death , programmed cell death , induction of programmed cell death , monovalent inorganic cation transport , death , negative regulation of transcription , regulation of phosphate metabolic process , cell cycle process , cell cycle phase , metal ion transport , negative regulation of cell growth , regulation of microtubule polymerization or depolymerization , positive regulation of microtubule polymerization or depolymerization , regulation of microtubule polymerization , positive regulation of microtubule polymerization , negative regulation of cellular biosynthetic process , positive regulation of protein complex assembly ,regulation of protein polymerization , positive regulation of protein polymerization , regulation of cellular component size , negative regulation of gene-specific transcription , regulation of gene-specific transcription , regulation of microtubule-based process , regulation of organelle organization , negative regulation of kinase activity , regulation of growth , regulation of cell proliferation , regulation of phosphorylation , negative regulation of phosphorylation ,regulation of apoptosis , positive regulation of apoptosis , regulation of programmed cell death , positive regulation of programmed cell death , negative regulation of catalytic activity , regulation of protein complex assembly , regulation of kinase activity , ear development , regulation of cellular component biogenesis , negative regulation of molecular function , regulation of transcription , negative regulation of cyclin-dependent protein kinase activity , negative regulation of cell cycle , negative regulation of cell size , regulation of protein kinase activity , negative regulation of transcription , DNA-dependent , negative regulation of growth , negative regulation of nucleobase , nucleoside , nucleotide and nucleic acid metabolic process , negative regulation of phosphate metabolic process , autophagic cell death , inner ear development , regulation of epithelial cell proliferation , negative regulation of epithelial cell proliferation , neurological system process , cognition , sensory perception of mechanical stimulus , positive regulation of cellular component organization , negative regulation of nitrogen compound metabolic process , regulation of phosphorus metabolic process , regulation of RNA metabolic process , negative regulation of RNA metabolic process ,regulation of cell motion , negative regulation of cell motion , interphase , interphase of mitotic cell cycle , regulation of transferase activity , negative regulation of transferase activity , regulation of cytoskeleton organization , positive regulation of cytoskeleton organization , regulation of cell cycle , regulation of microtubule cytoskeleton organization ,

Nucleus. Cytoplasm. Endosome . Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-198 , binds 14-3-3 , translocates to the cytoplasm and promotes cell cycle progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in translocation to the cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus on phosphorylation of Tyr-88 and Tyr-89. Colocalizes at the endosome with SNX6; this leads to lysosomal degradation (By similarity) . .