Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Microarray analysis of Saccharomyces cerevisiae expressing the Hsp90 mutant hsc82-W296A

ABSTRACT: Altered mRNA levels of HBT1 were observed in S. cerevisiae cells expressing hsc82-W296A compared to WT HSC82. We conducted microarray analysis to determine the extent of other changes in that strain. The yeast strain used contained chromosomal deletions of HSC82 and HSP82. WT HSC82 or hsc82-W296A was supplied on a plasmid so that it was the only Hsp90 present in the cell. Yeast were grown overnight in rich media at 30Â° and harvested during exponential growth phase. RNA was harvested from three cultures expressing WT Hsc82 and 3 cultures expressing the Hsp90 mutant..

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Jill Johnson

PROVIDER: E-GEOD-34757 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of an Hsp90 mutation that selectively disrupts cAMP/PKA signaling in Saccharomyces cerevisiae.

Flom Gary A GA Langner Ewa E Johnson Jill L JL

Current genetics 20120330 3

The molecular chaperone Hsp90 cooperates with multiple cochaperone proteins as it promotes the folding and activation of diverse client proteins. Some cochaperones regulate the ATPase activity of Hsp90, while others appear to promote Hsp90 interaction with specific types of client proteins. Through its interaction with the adenylate cyclase Cyr1, the Sgt1 cochaperone modulates the activity of the cAMP pathway in Saccharomyces cerevisiae. A specific mutation in yeast Hsp90, hsc82-W296A, or a muta ...[more]

PMID: 22461145

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Project description:The capacity to sense and transduce temperature signals pervades all aspects of biology, and temperature exerts powerful control over the development and virulence of diverse pathogens. In the leading fungal pathogen of humans, Candida albicans, temperature has a profound impact on morphogenesis, a key virulence trait. Many cues that induce the transition from yeast to filamentous growth are contingent on a minimum temperature of 37ÂºC, while further elevatation to 39ÂºC serves as an independent inducing cue. The molecular chaperone Hsp90 is a key regulator of C. albicans temperature-dependent morphogenesis, as induction of filamentous growth requires relief from Hsp90-mediated repression of the morphogenetic program. Compromise of Hsp90 function genetically, pharmacologically, or by elevated temperature induces filamentation in a manner that depends on protein kinase A (PKA) signaling, but is independent of the terminal transcription factor, Efg1. Here, we determine that despite morphological and regulatory differences, inhibition of Hsp90 induces a transcriptional profile similar to that induced by other filamentation cues, and does so in a manner that is independent of Efg1. Further, we identify Hms1 as a transcriptional regulator required for morphogenesis induced by elevated temperature or compromise of Hsp90 function. Hms1 functions downstream of the cyclin Pcl, and the cyclin-dependent kinase Pho85, both of which are required for temperature-dependent filamentation. Upon Hsp90 inhibition, Hms1 binds to DNA elements involved in filamentous growth, including UME6 and RBT5, and regulates their expression, providing a mechanism through which Pho85, Pcl1, and Hms1 govern morphogenesis. Consistent with the importance of morphogenetic flexibility with virulence, deletion of C. albicans HMS1 attenuates virulence in a metazoan model of infection. Thus, we establish a new mechanism through which Hsp90 orchestrates C. albicans morphogenesis, and define novel regulatory circuitry governing a temperature-dependent developmental program, with broad implications for temperature sensing and virulence of microbial pathogens. Two-color experimental design testing the effect of geldanamycin on wild type of delta-efg1 cells. RNA from each replicate came from independent cultures.

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Dataset Information

Microarray analysis of Saccharomyces cerevisiae expressing the Hsp90 mutant hsc82-W296A

Publications

Identification of an Hsp90 mutation that selectively disrupts cAMP/PKA signaling in Saccharomyces cerevisiae.

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