Dynamic Sumoylation of a Conserved Transcription Corepressor Prevents Persistent Inclusion Formation during Hyperosmotic Stress.
Dynamic Sumoylation of a Conserved Transcription Corepressor Prevents Persistent Inclusion Formation during Hyperosmotic Stress.
复制标题
DOI：
10.1371/journal.pgen.1005809
复制
发表时间：
2016-01
期刊：
影响因子：
4.5
通讯作者：
Gardner RG
中科院分区：
文献类型：
--
作者：
Oeser ML;Amen T;Nadel CM;Bradley AI;Reed BJ;Jones RD;Gopalan J;Kaganovich D;Gardner RG
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. Cells have evolved complex stress responses to cope with environmental challenges that could otherwise inflict severe damage on the molecules essential for life. Stress responses must ameliorate the immediate damage caused by stress exposure and also adjust metabolic capacity, gene expression output, and other cellular functions to protect against further damage that could be incurred by prolonged exposure to stress. Posttranslational protein modifications are a major means by which cells respond to changing environmental conditions. These modifications can alter the function, localization, and molecular interactions of their target proteins. In addition, evidence is emerging that some posttranslational modifications may also change the physical characteristics of target proteins. In this study, we present evidence that during hyperosmotic stress, a condition known to induce protein misfolding, cells rapidly but transiently use the small ubiquitin-modifier SUMO to protect against persistent inclusion formation of a conserved transcriptional repressor complex. We propose that this rapid protective action via posttranslational modification enables optimal gene regulation during the cellular response to hyperosmotic stress.
