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.
Highlights
Throughout their lives, cells will be exposed to a variety of stresses: extreme temperatures, altered osmolarity, hypoxia, free radicals, infections, and genotoxic insults
Stress responses must ameliorate the immediate damage caused by stress exposure and adjust metabolic capacity, gene expression output, and other cellular functions to protect against further damage that could be incurred by prolonged exposure to stress
We wished to avoid any spurious issues that could occur due to overexpression, so we opted for an endogenous expression approach to examine the temporal changes in sumoylation that occur during application of different stresses
Summary
Throughout their lives, cells will be exposed to a variety of stresses: extreme temperatures, altered osmolarity, hypoxia, free radicals, infections, and genotoxic insults. Exposure to these stresses can deleteriously damage the structures of essential biomolecules such as DNA, RNA, and proteins. Stress responses initiate cellular programs that rapidly alter specific protein activities to cope with the immediate damage caused by acute exposure to stress. They adjust gene expression and metabolism to protect against further damage that can be incurred by prolonged exposure to stress. Many human diseases (e.g. diabetes, heart disease, cancer, and neurodegeneration) result from, or cause cellular stress [1]
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