M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.

Cyclin-dependent kinases, or CDKs, work in concert with cyclins to control cell cycle transitions. M-CDK, a complex of CDK1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from G₂ to M phase.

M cyclin promotes M phase events—such as mitotic spindle formation, sister chromatid attachment to opposite spindle poles, chromosome condensation, nuclear envelope breakdown, and actin cytoskeleton and Golgi apparatus rearrangement. By promoting these processes, M cyclin drives the transition into the M phase.

Like other cyclins, M cyclin levels fluctuate during the cell cycle. CDK levels, however, remain relatively stable. In most cells (embryonic cells are an exception), M cyclin gene transcription increases, and M cyclin accumulates as the cell approaches the G₂/M transition. The accumulated M cyclin binds to CDK, forming M-CDK complexes. The M-CDKs are primed to trigger M phase events upon activation, largely by Cdc25.

Active M-CDK enables the transition into mitosis by phosphorylating proteins that enable several early mitotic processes. However, M-CDK is not the only protein kinase that regulates this transition. Polo-like kinases and Aurora kinases, for example, also contribute to early mitotic processes.

Plk1 is a polo-like kinase necessary for the normal bipolar formation of the mitotic spindle. Plk1 phosphorylates proteins that help separate the spindle poles. Aurora-A also regulates proteins involved in forming and stabilizing the mitotic spindle, while Aurora-B allows sister chromatids to attach to the spindle. Together, M-CDK and other protein kinases help regulate the transition between the G₂ and M phases of the cell cycle.