A Whi7-anchored loop controls the G1 Cdk-cyclin complex at start.
Cells commit to a new cell cycle at Start by activation of the G1 Cdk-cyclin complex which, in turn, triggers a genome-wide transcriptional wave that executes the G1/S transition. In budding yeast, the Cdc28-Cln3 complex is regulated by an ER-retention mechanism that is important for proper cell size control. We ... have isolated small-cell-size CDC28 mutants showing impaired retention at the ER and premature accumulation of the Cln3 cyclin in the nucleus. The differential interactome of a quintuple Cdc28(wee) mutant pinpointed Whi7, a Whi5 paralog targeted by Cdc28 that associates to the ER in a phosphorylation-dependent manner. Our results demonstrate that the Cln3 cyclin and Whi7 act in a positive feedback loop to release the G1 Cdk-cyclin complex and trigger Start once a critical size has been reached, thus uncovering a key nonlinear mechanism at the earliest known events of cell-cycle entry.
Mesh Terms:
CDC28 Protein Kinase, S cerevisiae, Cyclins, Endoplasmic Reticulum, G1 Phase, Mutation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
CDC28 Protein Kinase, S cerevisiae, Cyclins, Endoplasmic Reticulum, G1 Phase, Mutation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Mol. Cell
Date: Jan. 09, 2014
PubMed ID: 24374311
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