Cyclin-dependent kinase inhibitor 1B

Definition

Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. 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.

References:

[1]. Arpita Ray, et al. p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes. Mol Cell Biol. 2009 Feb;29(4):986-99. [Content Brief]

[2]. Denise A McGrath, et al. Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO proteins. EMBO J. 2017 Aug 1;36(15):2251-2262. [Content Brief]

[3]. Matthias Grimmler, et al. Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. Cell. 2007 Jan 26;128(2):269-80. [Content Brief]

[4]. N Ishida, et al. 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. [Content Brief]

[5]. Incheol Shin, et al. 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. [Content Brief]

[6]. Laurence Bockstaele, et al. 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. [Content Brief]

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