The morphogenesis checkpoint in Saccharomyces cerevisiae: Cell cycle control of Swe1p degradation by Hsl1p and Hsl7p

In Saccharomyces cerevisiae, the Wee1 family kinase Swe1p is normally stabl e during G(1) and S phases but is unstable during G(2) and M phases due to ubiquitination and subsequent degradation, However, perturbations of the ac tin cytoskeleton lead to a stabilization and accumulation of Swe1p. This re sponse constitutes part of a morphogenesis checkpoint that couples cell cyc le progression to proper bud formation, but the basis for the regulation of Swe1p degradation by the morphogenesis checkpoint remains unknown. Previou s studies have identified a protein kinase, Hsl1p, and a phylogenetically c onserved protein of unknown function, Hsl7p, as putative negative regulator s of Swe1p, We report here that Hsl1p and Hsl7p act in concert to target Sw e1p for degradation. Both proteins are required for Swe1p degradation durin g the unperturbed cell cycle, and excess Hsl1p accelerates Swe1p degradatio n in the G(2)-M phase. Hsl1p accumulates periodically during the cell cycle and promotes the periodic phosphorylation of Hsl7p, Hsl7p can be detected in a complex with Swe1p in cell lysates, and the overexpression of Hsl7p or Hsl1p produces an effective override of the G(2) arrest imposed by the mor phogenesis checkpoint. These findings suggest that Hsl1p and Hsl7p interact directly with Swe1p to promote its recognition by the ubiquitination compl ex, leading ultimately to its destruction.