Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone

Rongmin Zhao; Mike Davey; Ya-Chieh Hsu; Pia Kaplanek; Amy Tong; Ainslie B Parsons; Nevan Krogan; Gerard Cagney; Duy Mai; Jack Greenblatt; Charles Boone; Andrew Emili; Walid A Houry

doi:10.1016/j.cell.2004.12.024

Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone

Cell. 2005 Mar 11;120(5):715-27. doi: 10.1016/j.cell.2004.12.024.

Authors

Rongmin Zhao¹, Mike Davey, Ya-Chieh Hsu, Pia Kaplanek, Amy Tong, Ainslie B Parsons, Nevan Krogan, Gerard Cagney, Duy Mai, Jack Greenblatt, Charles Boone, Andrew Emili, Walid A Houry

Affiliation

¹ Department of Biochemistry, Medical Sciences Building, 1 King's College Circle, University of Toronto, Toronto, ON, M5S 1A8, Canada.

PMID: 15766533
DOI: 10.1016/j.cell.2004.12.024

Abstract

Physical, genetic, and chemical-genetic interactions centered on the conserved chaperone Hsp90 were mapped at high resolution in yeast using systematic proteomic and genomic methods. Physical interactions were identified using genome-wide two hybrid screens combined with large-scale affinity purification of Hsp90-containing protein complexes. Genetic interactions were uncovered using synthetic genetic array technology and by a microarray-based chemical-genetic screen of a set of about 4700 viable yeast gene deletion mutants for hypersensitivity to the Hsp90 inhibitor geldanamycin. An extended network, consisting of 198 putative physical interactions and 451 putative genetic and chemical-genetic interactions, was found to connect Hsp90 to cofactors and substrates involved in a wide range of cellular functions. Two novel Hsp90 cofactors, Tah1 (YCR060W) and Pih1 (YHR034C), were also identified. These cofactors interact physically and functionally with the conserved AAA(+)-type DNA helicases Rvb1/Rvb2, which are key components of several chromatin remodeling factors, thereby linking Hsp90 to epigenetic gene regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / metabolism
Benzoquinones
Chromosome Mapping / methods
Coenzymes / genetics
Coenzymes / isolation & purification
Coenzymes / metabolism
DNA Helicases
Drug Resistance, Fungal / genetics
Epigenesis, Genetic / genetics
Gene Expression Regulation, Fungal / genetics
Genome, Fungal
HSP90 Heat-Shock Proteins / chemistry
HSP90 Heat-Shock Proteins / genetics*
HSP90 Heat-Shock Proteins / metabolism*
Lactams, Macrocyclic
Mass Spectrometry
Molecular Chaperones / chemistry
Molecular Chaperones / genetics*
Molecular Chaperones / metabolism*
Oligonucleotide Array Sequence Analysis
Proteomics / methods
Quinones / pharmacology
RNA Helicases / metabolism
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / genetics*
Saccharomyces cerevisiae Proteins / metabolism*
Transcription Factors
Two-Hybrid System Techniques

Substances

Benzoquinones
Coenzymes
HSP82 protein, S cerevisiae
HSP90 Heat-Shock Proteins
Lactams, Macrocyclic
Molecular Chaperones
Quinones
Saccharomyces cerevisiae Proteins
Tah1 protein, S cerevisiae
Transcription Factors
Adenosine Triphosphatases
RVB1 protein, S cerevisiae
RVB2 protein, S cerevisiae
DNA Helicases
RNA Helicases
geldanamycin