title: Pkc1 and the upstream elements of the cell integrity pathway in Saccharomyces cerevisiae, Rom2 and Mtl1, are required for cellular responses to oxidative stress.
abstract: In this study we analyze the participation of the PKC1-MAPK cell integrity pathway in cellular responses to oxidative stress in Saccharomyces cerevisiae. Evidence is presented demonstrating that only Pkc1 and the upstream elements of the cell integrity pathway are essential for cell survival upon treatment with two oxidizing agents, diamide and hydrogen peroxide. Mtl1 is characterized for the first time as a cell-wall sensor of oxidative stress. We also show that the actin cytoskeleton is a cellular target for oxidative stress. Both diamide and hydrogen peroxide provoke a marked depolarization of the actin cytoskeleton, being Mtl1, Rom2 and Pkc1 functions all required to restore the correct actin organization. Diamide induces the formation of disulfide bonds in newly secreted cell-wall proteins. This mainly provokes structural changes in the cell outer layer, which activate the PKC1-MAPK pathway and hence the protein kinase Slt2. Our results led us to the conclusion that Pkc1 activity is required to overcome the effects of oxidative stress by: (i) enhancing the machinery required to repair the altered cell wall and (ii) restoring actin cytoskeleton polarity by promoting actin cable formation.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Alcalde Rovira Roure 44, Universitat de Lleida, Lleida 25198, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Vilella
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
authors.forename: Jordi
authors.initials: J
authors.lastname: Torres
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: de la Torre-Ruiz
mesh_terms: D001483:Base Sequence; D002470:Cell Survival; D002473:Cell Wall / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D003958:Diamide / Q000494:pharmacology; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006867:Hydrolases / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C464845:BBC1 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors; C490929:ROM2 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D003958:Diamide; C037833:zymolyase; D006861:Hydrogen Peroxide; C490702:PKC1 protein, S cerevisiae; D011493:Protein Kinase C; D006867:Hydrolases