Synthesized peptide derived from human p27Kip1 AA range: 100-198

This antibody detects endogenous levels of p27Kip1 protein.

CDKN1B KIP1

Cyclin-dependent kinase inhibitor 1B

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

This gene encodes a cyclin-dependent kinase inhibitor , which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes , and thus controls the cell cycle progression at G1. The degradation of this protein , which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes , is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4) . [provided by RefSeq , Apr 2014] ,

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. ,

Nuclear

>>Endocrine resistance ;
>>ErbB signaling pathway ;
>>HIF-1 signaling pathway ;
>>FoxO signaling pathway ;
>>Cell cycle ;
>>PI3K-Akt signaling pathway ;
>>AGE-RAGE signaling pathway in diabetic complications ;
>>Cushing syndrome ;
>>Measles ;
>>Human papillomavirus infection ;
>>Epstein-Barr virus infection ;
>>Pathways in cancer ;
>>Transcriptional misregulation in cancer ;
>>Viral carcinogenesis ;
>>MicroRNAs in cancer ;
>>Prostate cancer ;
>>Chronic myeloid leukemia ;
>>Small cell lung cancer ;
>>Gastric cancer