Accumulation of misfolded protein in the endoplasmic reticulum (ER) causes stress. The unfolded protein response (UPR), a transcriptional induction pathway, is activated to relieve ER stress. Although UPR is not essential for viability, UPR-deficient cells are more sensitive to ER stress; ire1Delta cells cannot grow when challenged with tunicamycin or by overexpression of misfolded CPY(*). In these cells, multiple functions are defective, including translocation, ER-associated degradation (ERAD), and ER-to-Golgi transport. We tested whether heat shock response (HSR) can relieve ER stress. Using a constitutively active Hsf1 transcription factor to induce HSR without temperature shift, we find that HSR rescues growth of stressed ire1Delta cells, and partially relieves defects in translocation and ERAD. Cargo-specific effects of constitutively active Hsf1 on ER-to-Golgi transport are correlated with enhanced protein levels of the respective cargo receptors. In vivo, HSR is activated by ER stress, albeit to a lower level than that caused by heat. Genomic analysis of HSR targets reveals that >25% have function in common with UPR targets. We propose that HSR can relieve stress in UPR-deficient cells by affecting multiple ER activities.
Pubmed ID: 18323774 RIS Download
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A curated database that provides comprehensive integrated biological information for Saccharomyces cerevisiae along with search and analysis tools to explore these data. SGD allows researchers to discover functional relationships between sequence and gene products in fungi and higher organisms. The SGD also maintains the S. cerevisiae Gene Name Registry, a complete list of all gene names used in S. cerevisiae which includes a set of general guidelines to gene naming. Protein Page provides basic protein information calculated from the predicted sequence and contains links to a variety of secondary structure and tertiary structure resources. Yeast Biochemical Pathways allows users to view and search for biochemical reactions and pathways that occur in S. cerevisiae as well as map expression data onto the biochemical pathways. Literature citations are provided where available.
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