Dataset Information

CDK5-Cyclin B1 regulates mitotic progression and fidelity

ABSTRACT: Mammalian cell cycle is driven by several CDK-cyclin complexes, with CDK1/cyclin B1 (CCNB1) being the one that is essential for mitotic entry and progression. CDK5 is not considered a typical CDK due to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p39. We previously showed that CDK5 is active in mitosis and here we demonstrate that CCNB1 is the mitotic activator of CDK5. Using independent chemical genetic approaches to specifically abrogate CDK5 at the onset of and throughout mitosis, we observe mitotic defects, nuclear atypia, and significant alterations in the mitotic phospho-proteome. Importantly, the disruption of the CDK5-CCNB1 complex phenocopies CDK5 abrogation. Together, our results demonstrate that CCNB1 partners with both CDK5 and CDK1 to drive mitosis, defines CDK5-CCNB1 as a canonical cell cycle CDK/cyclin complex and describes the role of CDK5-CCNB1 complex in ensuring mitotic fidelity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Jacob Kennedy

LAB HEAD: Dipanjan Chowdhury

PROVIDER: PXD038386 | Pride | 2025-08-04

REPOSITORIES: Pride

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			Action	DRS
	XZ061421_061621_GLBL_Fxn_01.raw	Raw
	XZ061421_061621_GLBL_Fxn_02.raw	Raw
	XZ061421_061621_GLBL_Fxn_03.raw	Raw
	XZ061421_061621_GLBL_Fxn_04.raw	Raw
	XZ061421_061621_GLBL_Fxn_05.raw	Raw

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CDK5-cyclin B1 regulates mitotic fidelity.

Zheng Xiao-Feng XF Sarkar Aniruddha A Lotana Humphrey H Syed Aleem A Nguyen Huy H Ivey Richard G RG Kennedy Jacob J JJ Whiteaker Jeffrey R JR Tomasik Bartłomiej B Huang Kaimeng K Li Feng F D'Andrea Alan D AD Paulovich Amanda G AG Shah Kavita K Spektor Alexander A Chowdhury Dipanjan D

Nature 20240904 8031

CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression<sup>1</sup>. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p39<sup>2</sup>. Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mito ...[more]

PMID: 39232161

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Project description:This model is from the article: Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast. Queralt E, Lehane C, Novak B, Uhlmann F. Cell. 2006 May 19;125(4):719-32. 16713564 , Abstract: After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14. How Net1 is phosphorylated specifically in anaphase, when mitotic kinase activity starts to decline, has remained unexplained. Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase. The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines. These findings allow us to present a new quantitative model for mitotic exit in budding yeast. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team. For more information see the terms of use . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.