| Structural highlights
Disease
CDN1B_HUMAN 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.[1]
Function
CDN1B_HUMAN Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.[2] [3] [4] [5] [6]
References
- ↑ Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, Fend F, Graw J, Atkinson MJ. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15558-63. Epub 2006 Oct 9. PMID:17030811 doi:0603877103
- ↑ Ishida N, Kitagawa M, Hatakeyama S, Nakayama K. Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J Biol Chem. 2000 Aug 18;275(33):25146-54. PMID:10831586 doi:10.1074/jbc.M001144200
- ↑ Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J, Arteaga CL. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med. 2002 Oct;8(10):1145-52. Epub 2002 Sep 16. PMID:12244301 doi:10.1038/nm759
- ↑ Bockstaele L, Kooken H, Libert F, Paternot S, Dumont JE, de Launoit Y, Roger PP, Coulonval K. Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors". Mol Cell Biol. 2006 Jul;26(13):5070-85. PMID:16782892 doi:10.1128/MCB.02006-05
- ↑ Ray A, James MK, Larochelle S, Fisher RP, Blain SW. p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes. Mol Cell Biol. 2009 Feb;29(4):986-99. doi: 10.1128/MCB.00898-08. Epub 2008 Dec, 15. PMID:19075005 doi:10.1128/MCB.00898-08
- ↑ Grimmler M, Wang Y, Mund T, Cilensek Z, Keidel EM, Waddell MB, Jakel H, Kullmann M, Kriwacki RW, Hengst L. Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. Cell. 2007 Jan 26;128(2):269-80. PMID:17254966 doi:S0092-8674(06)01645-X
|
