ClbCDK

ClbCDK refers to the cyclin-dependent kinase complexes formed by the B-type cyclins Clb1 through Clb6 together with the essential yeast CDK, Cdc28 (the functional homolog of CDK1 in other organisms). In Saccharomyces cerevisiae, these Clb–Cdc28 complexes coordinate progression through late cell cycle events, notably S phase and mitosis, with distinct Clb cyclins promoting different windows of activity. Cln-CDKs regulate the G1/S transition, while Clb-CDKs drive DNA replication licensing, spindle assembly, chromosome condensation, and mitotic progression.

The activity and substrate specificity of ClbCDKs depend on which Clb cyclin is bound to Cdc28. Clb5 and Clb6 are primarily active during S phase and promote origin firing, whereas Clb1 through Clb4 function mainly in G2 and M phase to drive mitotic entry and progression. Some overlap exists among Clb members, reflecting redundancy and specialization in timing. Clb–CDK activity is tightly controlled by the regulated synthesis and degradation of Clb cyclins, largely through the APC/C ubiquitin ligase pathway, with activators such as Cdc20 and Cdh1 mediating targeted proteolysis at defined cell cycle points. CDK inhibitors, notably Sic1, can bind Clb–CDK complexes to prevent premature activity, and phosphorylation feedback loops further modulate activity.

ClbCDKs phosphorylate a broad set of substrates to coordinate key events, including initiation of DNA replication, spindle assembly and chromosome alignment, chromosome condensation, and orderly mitotic progression. Proper Clb–CDK regulation is essential for timing transitions between cell cycle phases and for successful mitotic exit when cyclins are degraded.

In research, ClbCDKs in budding yeast have served as foundational models for understanding cyclin-dependent kinase regulation, substrate specificity, and the orchestration of eukaryotic cell division.