| Autor: |
Oeser ML; 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., Amen T; 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., Nadel CM; Department of Pharmacology, University of Washington, Seattle, Washington, United States of America., Bradley AI; Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America., Reed BJ; Department of Pharmacology, University of Washington, Seattle, Washington, United States of America., Jones RD; Department of Pharmacology, University of Washington, Seattle, Washington, United States of America., Gopalan J; Department of Pharmacology, University of Washington, Seattle, Washington, United States of America., Kaganovich D; Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel., Gardner RG; 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. |
| Abstrakt: |
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. |
