title: The cell wall sensors Mtl1, Wsc1, and Mid2 are required for stress-induced nuclear to cytoplasmic translocation of cyclin C and programmed cell death in yeast.
abstract: Mtl1 is a member of a cell wall sensor family that monitors cell wall integrity in budding yeast. In response to cell wall stress, Mtl1 activates the cell wall integrity (CWI) MAP kinase pathway which transmits this signal to the nucleus to effect changes in gene expression. One target of the CWI MAP kinase is cyclin C, a negative regulator of stress response genes. CWI activation results in cyclin C relocalization from the nucleus to the cytoplasm where it stimulates programmed cell death (PCD) before it is destroyed. This report demonstrates that under low oxidative stress conditions, a combination of membrane sensors, Mtl1 and either Wsc1 or Mid2, are required jointly to transmit the oxidative stress signal to initiate cyclin C destruction. However, when exposed to elevated oxidative stress, additional pathways independent of these three sensor proteins are activated to destroy cyclin C. In addition, N-glycosylation is important for Mtl1 function as mutating the receptor residue (Asn42) or an enzyme required for synthesis of N-acetylglucosamine (Gfa1) reduces sensor activity. Finally, combining gfa1-1 with the cyclin C null allele induces a severe synthetic growth defect. This surprising result reveals a previously unknown genetic interaction between cyclin C and plasma membrane integrity.
authors.affiliation: Department of Molecular Biology, Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08055, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Jin
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Parshin
authors.forename: Ira
authors.initials: I
authors.lastname: Daly
authors.forename: Randy
authors.initials: R
authors.lastname: Strich
authors.forename: Katrina F
authors.initials: KF
authors.lastname: Cooper
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001216:Asparagine / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism*; D056745:Cyclin C / Q000378:metabolism; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D056745:Cyclin C; D047908:Intracellular Signaling Peptides and Proteins; C091625:MID2 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C550933:Mtl1 protein, S cerevisiae; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; C119383:SLG1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D001216:Asparagine; D006861:Hydrogen Peroxide; C098848:GFA1 protein, S cerevisiae; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)