SCFCdc4 Enables Mating Type Switching in Yeast by Cyclin-Dependent Kinase-Mediated Elimination of the Ash1 Transcriptional Repressor

Qingquan Liu, Brett Larsen, Marketa Ricicova, Stephen Orlicky, Hille Tekotte, Xiaojing Tang, Karen Craig, Adam Quiring, Thierry Le Bihan, Carl Hansen, Frank Sicheri, Mike Tyers

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

In the budding yeast Saccharomyces cerevisiae, mother cells switch mating types between a and alpha forms, whereas daughter cells do not. This developmental asymmetry arises because the expression of the HO endonuclease, which initiates the interconversion of a and alpha mating type cassettes, is extinguished by the daughter-specific Ash1 transcriptional repressor. When daughters become mothers in the subsequent cell cycle, Ash1 must be eliminated to enable a new developmental state. Here, we report that the ubiquitin ligase SCFCdc4 mediates the phosphorylation-dependent elimination of Ash1. The inactivation of SCFCdc4 stabilizes Ash1 in vivo, and consistently, Ash1 binds to and is ubiquitinated by SCFCdc4 in a phosphorylation-dependent manner in vitro. The mutation of a critical in vivo cyclin-dependent kinase (CDK) phosphorylation site (Thr290) on Ash1 reduces its ubiquitination and rate of degradation in vivo and decreases the frequency of mating type switching. Ash1 associates with active Cdc28 kinase in vivo and is targeted to SCFCdc4 in a Cdc28-dependent fashion in vivo and in vitro. Ash1 recognition by Cdc4 appears to be mediated by at least three phosphorylation sites that form two redundant diphosphorylated degrons. The phosphorylation-dependent elimination of Ash1 by the ubiquitin-proteasome system thus underpins developmental asymmetry in budding yeast.

Original languageEnglish
Pages (from-to)584-598
Number of pages15
JournalMolecular and Cellular Biology
Volume31
Issue number3
Early online date13 Jan 2011
DOIs
Publication statusPublished - 28 Feb 2011

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