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

Gary A Flom; Ewa Langner; Jill L Johnson

doi:10.1007/s00294-012-0373-7

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

Journal article

Peer reviewed

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

Gary A Flom, Ewa Langner and Jill L Johnson

Current genetics, Vol.58(3), pp.149-163

06/2012

DOI: https://doi.org/10.1007/s00294-012-0373-7

Handle:

https://hdl.handle.net/2376/112837

PMID: 22461145

Abstract

Antifungal Agents - pharmacology

Cyclic AMP-Dependent Protein Kinases - metabolism

Gene Expression Regulation, Fungal

Amino Acid Sequence

Morphogenesis - genetics

Signal Transduction

Saccharomyces cerevisiae - genetics

Saccharomyces cerevisiae Proteins - antagonists & inhibitors

Molecular Sequence Data

Up-Regulation - genetics

Saccharomyces cerevisiae Proteins - genetics

Saccharomyces cerevisiae - metabolism

HSP90 Heat-Shock Proteins - antagonists & inhibitors

Adaptor Proteins, Signal Transducing - genetics

Saccharomyces cerevisiae Proteins - metabolism

Macrolides - pharmacology

Protein Binding

Transcription, Genetic

HSP90 Heat-Shock Proteins - genetics

Mutation

Adaptor Proteins, Signal Transducing - metabolism

Cyclic AMP - metabolism

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 mutation in Sgt1, sgt1-K360E, resulted in altered transcription patterns genetically linked to the cAMP pathway. Hsp90 interacted with Cyr1 in vivo and the hsc82-W296A mutation resulted in reduced accumulation of Cyr1. Hsp90-Sgt1 interaction was altered by either the hsc82-W296A or sgt1-K360E mutation, suggesting defective Hsp90-Sgt1 cooperation leads to reduced Cyr1 activity. Microarray analysis of hsc82-W296A cells indicated that over 80 % of all transcriptional changes in this strain may be attributed to altered cAMP signaling. This suggests that a majority of the cellular defects observed in hsc82-W296A cells are due to altered interaction with one specific essential cochaperone, Sgt1 and one essential client, Cyr1. Together our results indicate that specific interaction of Hsp90 and Sgt1 with Cyr1 plays a key role in regulating gene expression, including genes involved in polarized morphogenesis.

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Title: Identification of an Hsp90 mutation that selectively disrupts cAMP/PKA signaling in Saccharomyces cerevisiae
Creators: Gary A Flom - Department of Biological Sciences, Center for Reproductive Biology, University of Idaho, Life Sciences South Room 252, P.O. Box 443051, Moscow, ID 83844-3051, USA
Ewa Langner
Jill L Johnson
Publication Details: Current genetics, Vol.58(3), pp.149-163
Academic Unit: UNKNOWN
Publisher: United States
Identifiers: 99900547635301842
Language: English
Resource Type: Journal article

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

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