Sic1mediated

Sic1mediated refers to cellular processes governed by Sic1, a cyclin-dependent kinase inhibitor in budding yeast (Saccharomyces cerevisiae). Sic1 acts as a stoichiometric inhibitor of S-phase CDKs and helps regulate the G1 to S phase transition by limiting premature activation of S-phase cyclin–CDK complexes.

In G1, phosphorylation of Sic1 by CDKs, notably Cln1/2–Cdc28, creates multiple phosphodegrons. This phosphorylation marks Sic1 for recognition by the SCF ubiquitin ligase complex (SCF(Cdc4)), leading to its ubiquitination and proteasomal degradation. As Sic1 is degraded, inhibition of S-phase CDKs is lifted, allowing Cdc28–Clb5/6 activity to drive DNA replication. Sic1 also binds to and inhibits Cln–CDK complexes, reinforcing the G1 arrest when appropriate.

Regulation of Sic1 levels integrates signaling inputs. Mating pheromone signaling (alpha factor) stabilizes Sic1 and maintains CDK inhibition, producing G1 arrest. Nutrient limitation and stress can influence Sic1 stability indirectly by altering CDK activity and SCF function. The timing of Sic1 degradation is therefore a critical checkpoint that couples cell growth to DNA replication.

Sic1-mediated control of the G1/S transition is essential for proper cell-cycle progression and genome stability in yeast. As a functional analogue of CKI proteins in other eukaryotes, Sic1 provides insight into conserved strategies cells use to restrain CDK activity until conditions are suitable for DNA synthesis.