title: Dynamic Sumoylation of a Conserved Transcription Corepressor Prevents Persistent Inclusion Formation during Hyperosmotic Stress.
abstract: Cells are often exposed to physical or chemical stresses that can damage the structures of essential biomolecules. Stress-induced cellular damage can become deleterious if not managed appropriately. Rapid and adaptive responses to stresses are therefore crucial for cell survival. In eukaryotic cells, different stresses trigger post-translational modification of proteins with the small ubiquitin-like modifier SUMO. However, the specific regulatory roles of sumoylation in each stress response are not well understood. Here, we examined the sumoylation events that occur in budding yeast after exposure to hyperosmotic stress. We discovered by proteomic and biochemical analyses that hyperosmotic stress incurs the rapid and transient sumoylation of Cyc8 and Tup1, which together form a conserved transcription corepressor complex that regulates hundreds of genes. Gene expression and cell biological analyses revealed that sumoylation of each protein directs distinct outcomes. In particular, we discovered that Cyc8 sumoylation prevents the persistence of hyperosmotic stress-induced Cyc8-Tup1 inclusions, which involves a glutamine-rich prion domain in Cyc8. We propose that sumoylation protects against persistent inclusion formation during hyperosmotic stress, allowing optimal transcriptional function of the Cyc8-Tup1 complex.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America.|Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Oeser
authors.affiliation: Alexander Grass Center for Bioengineering, Hebrew University of Jerusalem, Jerusalem, Israel.|Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Triana
authors.initials: T
authors.lastname: Amen
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Nadel
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America.
authors.forename: Amanda I
authors.initials: AI
authors.lastname: Bradley
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Reed
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Ramon D
authors.initials: RD
authors.lastname: Jones
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Janani
authors.initials: J
authors.lastname: Gopalan
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaganovich
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America.|Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Gardner
mesh_terms: D015966:Gene Expression Regulation, Fungal; D009997:Osmotic Pressure; D011401:Promoter Regions, Genetic; D040901:Proteomics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D058207:Sumoylation / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins