Cyclin Dependent Kinase Inhibitor 1B (CDKN1B)

CDKN4; KIP1; P27KIP1; p27; Cyclin-dependent kinase inhibitor p27

SPN	S146
HGNC	1785
MGI	104565
PubMed	22026581
RGD	69062
UniProt	P46527
Wiki	CDKN1B

Cyclin-dependent kinase inhibitor 1B is a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. 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. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle.

The p27^Kip1 gene has a DNA sequence similar to other members of the "Cip/Kip" family which include the p21^Cip1/Waf1 and p57^Kip2 genes. In addition to this structural similarity the "Cip/Kip" proteins share the functional characteristic of being able to bind several different classes of Cyclin and Cdk molecules.

Reference

"Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals."
Cell 78:59-66(1994) [PubMed] [Europe PMC] [Abstract]

"Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias."
Cancer Res. 55:1206-1210(1995) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation."
Genes Dev. 13:1181-1189(1999) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability."
J. Biol. Chem. 275:25146-25154(2000) [PubMed] [Europe PMC] [Abstract]

"A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression."
EMBO J. 21:3390-3401(2002) [PubMed] [Europe PMC] [Abstract]

"Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization."
J. Biol. Chem. 277:28706-28713(2002) [PubMed] [Europe PMC] [Abstract]

"Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer."
Nat. Med. 8:1136-1144(2002) [PubMed] [Europe PMC] [Abstract]

"PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization."
Nat. Med. 8:1145-1152(2002) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization."
J. Biol. Chem. 278:49254-49260(2003) [PubMed] [Europe PMC] [Abstract]

"Spy1 interacts with p27Kip1 to allow G1/S progression."
Mol. Biol. Cell 14:3664-3674(2003) [PubMed] [Europe PMC] [Abstract]

"Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer."
Cell Cycle 3:1074-1080(2004) [PubMed] [Europe PMC] [Abstract]

"Cdc2-cyclin E complexes regulate the G1/S phase transition."
Nat. Cell Biol. 7:831-836(2005) [PubMed] [Europe PMC] [Abstract]

"Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4."
Blood 107:1133-1140(2006) [PubMed] [Europe PMC] [Abstract]

"Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'."
Mol. Cell. Biol. 26:5070-5085(2006) [PubMed] [Europe PMC] [Abstract]

"Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein."
Mol. Cell. Biol. 26:5994-6004(2006) [PubMed] [Europe PMC] [Abstract]

"Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans."
Proc. Natl. Acad. Sci. U.S.A. 103:15558-15563(2006) [PubMed] [Europe PMC] [Abstract]

"p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2."
Cell 128:281-294(2007) [PubMed] [Europe PMC] [Abstract]

"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]

"Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels."
Cancer Res. 68:5076-5085(2008) [PubMed] [Europe PMC] [Abstract]

"p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes."
Mol. Cell. Biol. 29:986-999(2009) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control."
Oncogene 30:3502-3512(2011) [PubMed] [Europe PMC] [Abstract]

"Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I."
Cell. Signal. 25:2047-2059(2013) [PubMed] [Europe PMC] [Abstract]

"Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase."
Mol. Cell 49:1159-1166(2013) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex."
Nature 382:325-331(1996) [PubMed] [Europe PMC] [Abstract]

"Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase."
Mol. Cell 20:9-19(2005) [PubMed] [Europe PMC] [Abstract]

"Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases."
Cell 128:269-280(2007) [PubMed] [Europe PMC] [Abstract]

"PPM1H is a p27 phosphatase implicated in trastuzumab resistance."
Cancer Discov. 1:326-337(2011) [PubMed] [Europe PMC] [Abstract]

"A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization."
Hum. Mutat. 31:E1825-E1835(2010) [PubMed] [Europe PMC] [Abstract]