title: APC/CCdh1 specific degradation of Hsl1 and Clb2 is required for proper stress responses of S. cerevisiae.
abstract: Cdh1 activates the Anaphase Promoting Complex/Cyclosome (APC/C(Cdh1)) throughout G(1) to degrade key cell cycle proteins. Cdh1 is not essential for cell proliferation, in spite of the fact that overexpression of some its degradation substrates is highly toxic. We report here that cdh1Delta cells are sensitive to stresses that activate the CWI (Cell Wall Integrity) and Hog1 MAP kinase pathways. Stresses did not activate APC/C(Cdh1) and cellular sensitivity was thus clearly due to constitutively elevated substrate levels. To explore the contribution of stabilization of individual APC/C(Cdh1) substrates to stress sensitivity, we generated cell lines expressing stabilized substrate mutants under their endogenous promoters. Cells expressing stabilized Hsl1 were sensitive to caffeine and failed to activate the Slt2 pathway. Cells expressing partially stable Clb2 were particularly sensitive to different stresses, possibly due to reduced Sic1 levels. Cells expressing stabilized Cdc5 were much less stress sensitive. Interestingly sensitivity of cdh1Delta cells does not seem to be restricted to G(1) but is manifested also during S and G(2) when the APC/C(Cdh1) is inactive anyway. We thus hypothesize that a role of G(1) specific APC/C(Cdh1) activity is to reset substrate levels to enables appropriate regulation of substrate accumulation in the subsequent phases of the cell cycle.
authors.affiliation: The Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Kobi J
authors.initials: KJ
authors.lastname: Simpson-Lavy
authors.forename: Julia
authors.initials: J
authors.lastname: Sajman
authors.forename: Drora
authors.initials: D
authors.lastname: Zenvirth
authors.forename: Michael
authors.initials: M
authors.lastname: Brandeis
mesh_terms: D000222:Adaptation, Physiological; D064173:Anaphase-Promoting Complex-Cyclosome; D064200:Cdh1 Proteins; D002453:Cell Cycle; D019926:Cyclin B / Q000378:metabolism*; D016193:G1 Phase; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D012441:Saccharomyces cerevisiae / Q000166:cytology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D013312:Stress, Physiological; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*
chemical_list: C577583:CDH1 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D064200:Cdh1 Proteins; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C106494:HSL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae