Sic1

Sic1, a protein, is a stoichiometric inhibitor of Cdk1-Clb (B-type cyclins) complexes in the budding yeast Saccharomyces cerevisiae. Because B-type cyclin-Cdk1 complexes are the drivers of S-phase initiation, Sic1 prevents premature S-phase entry. Multisite phosphorylation of Sic1 is thought to time Sic1 ubiquitination and destruction, and by extension, the timing of S-phase entry.

Role of Sic1 in the cell cycle control

In the G1 phase of the cell cycle, Sic1 binds tightly to the Cdc28-Clb complex and inhibits it. Low Cdc28-Clb activity leads to the disassembly of the mitotic spindle, the assembly of the prereplicative complex and initiation of bud formation in yeast.

At the START point in the yeast cell cycle, the G1-cyclins Cln3, Cln1 and Cln 2 activate Cdc28. The activated complex will phosphorylate Sic1 at multiple sites which leads to its degradation by the SCF complex. When Sic1 is degraded, the Cdc28-Clb complex is no longer inhibited and the cell can enter the S/M-phase. Thus Sic1 inactivation is essential for transition into S phase (Fig.1).