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