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Genetics Dec (2006); 174(4):1825-39
The Cdc34-SCF Ubiquitination Complex Mediates Saccharomyces cerevisiae Cell Wall Integrity-
Varelas X, Stuart D, Ellison MJ, Ptak C
Institute for Biomolecular Design, University of Alberta, Edmonton, Alberta T6G 2H7, Canada-
Abstract: To identify novel functions for the Cdc34-SCF ubiquitination complex, we analyzed genomewide transcriptional profiles of cdc53-1 and cdc34-2 Saccharomyces cerevisiae mutants- This analysis revealed altered expression for several gene families, including genes involved in the regulation of cell wall organization and biosynthesis- This led us to uncover a role for the Cdc34-SCF complex in the regulation of cell wall integrity- In support of this, cdc53-1 and cdc34-2 mutants exhibit phenotypes characteristic of cell wall integrity mutants, such as SDS sensitivity and temperature-sensitive suppression by osmotic stabilizers- Examination of these mutants revealed defects in their induction of Slt2 phosphorylation, indicating defects in Pkc1-Slt2 MAPK signaling- Consistent with this, synthetic genetic interactions were observed between the genes encoding the Cdc34-SCF complex and key components of the Pck1-Slt2 MAPK pathway- Further analysis revealed that Cdc34-SCF mutants have reduced levels of active Rho1, suggesting that these defects stem from the deregulated activity of the Rho1 GTPase- Altering the activity of Rho1 via manipulation of the Rho1-GAPs LRG1 or SAC7 affected Cdc34-SCF mutant growth- Strikingly, however, deletion of LRG1 rescued the growth defects associated with Cdc34-SCF mutants, whereas deletion of SAC7 enhanced these defects- Given the differential roles that these GAPs play in the regulation of Rho1, these observations indicate the importance of coordinating Cdc34-SCF activity with specific Rho1 functions-
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.