CAK1

Cak1, short for CDK-activating kinase 1, is a protein kinase found in Saccharomyces cerevisiae that functions as a primary CDK-activating kinase in budding yeast. Its activity places CDKs into a catalytically competent state by promoting phosphorylation of their activation loop (T-loop), enabling them to respond to regulatory cyclins and drive cell cycle progression.

In yeast, the essential substrate of Cak1 is Cdc28, the central CDK that partners with different cyclins to govern transitions through G1, S, and M phases. By phosphorylating the T-loop of Cdc28, Cak1 enables proper CDK activation, which is a prerequisite for mitotic entry and other cell cycle transitions. This activation mechanism differs from higher eukaryotes, where CDK-activating activity is predominantly provided by CDK7 as part of the TFIIH complex; in yeast, Cak1 functions independently to activate Cdc28.

Cak1 is a serine/threonine kinase that localizes to both cytoplasmic and nuclear compartments, reflecting its role in controlling CDK activity that influences various cell cycle events. Its activity is subject to regulation by cellular cues and protein–protein interactions with CDKs and cyclins, and alterations in CAK1 can lead to cell cycle defects and reduced growth.

Genetic and biochemical studies have established CAK1 as a conserved component of the CDK activation machinery in yeast. The gene CAK1 and its protein product provide a model for understanding CDK regulation, with broader relevance to conserved CDK activation mechanisms across eukaryotes.