cdc28

Cdc28 is the essential cyclin-dependent kinase that drives the cell cycle in budding yeast (Saccharomyces cerevisiae). It is the catalytic subunit of the Cdc28 kinase and is functionally homologous to CDK1 in other eukaryotes. Cdc28 forms active complexes with a family of cyclins, including the G1 cyclins Cln1, Cln2, and Cln3, as well as the S, G2, and M phase cyclins Clb1–Clb6. The specific cyclin partner determines substrate recognition and the cell-cycle phase in which Cdc28 acts.

Activation and regulation of Cdc28 depend on several layers of control. The activation loop contains Thr169, which is phosphorylated by the CDK-activating kinase Cak1 to generate an active kinase. Inhibitory phosphorylation at Tyr19 by the Swe1 kinase temporarily suppresses activity, with the Mih1 phosphatase removing this phosphate to reactivate the enzyme. In addition, inhibitors such as Sic1 regulate progression through Start by preventing Clb–Cdc28 activity until appropriate signals lead to Sic1 degradation, enabling S-phase entry.

Cell-cycle roles of Cdc28 are mediated through its cyclin partners. Cln–Cdc28 activity promotes the G1/S transition and the transcriptional program for DNA replication. Clb5/6–Cdc28 drives S-phase progression, while Clb1–Clb4–Cdc28 governs mitotic events, including spindle formation, chromosome alignment, and cytokinesis. The network integrates signals related to cell growth and DNA integrity to coordinate orderly progression through the cell cycle.

Genetics and model relevance: CDC28 is essential for viability in budding yeast, and temperature-sensitive cdc28 mutants arrest at various points in the cell cycle, highlighting its central regulatory role. The Cdc28–cyclin system serves as a foundational model for understanding CDK regulation and cyclin-dependent control of eukaryotic cell division.