Chen Y~Koong AC, 2005

Pubmed ID 16380504
Title Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae.
Authors Yijun Chen, Douglas E Feldman, Changchun Deng, James A Brown, Anthony F De Giacomo, Allison F Gaw, Gongyi Shi, Quynh T Le, J Martin Brown, Albert C Koong
Abstract Hypoxia activates all components of the unfolded protein response (UPR), a stress response initiated by the accumulation of unfolded proteins within the endoplasmic reticulum (ER). Our group and others have shown previously that the UPR, a hypoxia-inducible factor-independent signaling pathway, mediates cell survival during hypoxia and is required for tumor growth. Identifying new genes and pathways that are important for survival during ER stress may lead to the discovery of new targets in cancer therapy. Using the set of 4,728 homozygous diploid deletion mutants in budding yeast, Saccharomyces cerevisiae, we did a functional screen for genes that conferred resistance to ER stress-inducing agents. Deletion mutants in 56 genes showed increased sensitivity under ER stress conditions. Besides the classic UPR pathway and genes related to calcium homeostasis, we report that two additional pathways, including the SLT2 mitogen-activated protein kinase (MAPK) pathway and the osmosensing MAPK pathway, were also required for survival during ER stress. We further show that the SLT2 MAPK pathway was activated during ER stress, was responsible for increased resistance to ER stress, and functioned independently of the classic IRE1/HAC1 pathway. We propose that the SLT2 MAPK pathway is an important cell survival signaling pathway during ER stress. This study shows the feasibility of using the yeast deletion pool to identify relevant mammalian orthologues of the UPR.
Citation Mol. Cancer Res. 2005; 3:669-77


Download the list of datasets
Papers Phenotype Conditions Collection Tested mutants Data Details
Chen Y~Koong AC, 2005 growth (relative abundance in pooled culture) tunicamycin [1 ug/ml] hom ~4,728 Discrete
Chen Y~Koong AC, 2005 growth (relative abundance in pooled culture) dithiothreitol [4 mM] hom ~4,728 Discrete
Chen Y~Koong AC, 2005 growth (relative abundance in pooled culture) beta-mercaptoethanol [30 mM] hom ~4,728 Discrete

Curation history

Oct. 17, 2014 Tested strains to request.
Oct. 17, 2014 Data to request.
April 4, 2016 Tested strains requested.
April 4, 2016 Data requested.
Aug. 16, 2016 Tested strains requested.
Aug. 16, 2016 Data requested.
Aug. 17, 2016 Tested strains not available.
Aug. 17, 2016 Data not available.