Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone.
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.
Zhao
Rongmin
R
Department of Biochemistry, Medical Sciences Building, 1 King's College Circle, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Davey
Mike
M
Hsu
Ya-Chieh
YC
Kaplanek
Pia
P
Tong
Amy
A
Parsons
Ainslie B
AB
Krogan
Nevan
N
Cagney
Gerard
G
Mai
Duy
D
Greenblatt
Jack
J
Boone
Charles
C
Emili
Andrew
A
Houry
Walid A
WA
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016227:Benzoquinones; D002874:Chromosome Mapping / Q000379:methods; D003067:Coenzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004265:DNA Helicases; D025141:Drug Resistance, Fungal / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D016681:Genome, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D047029:Lactams, Macrocyclic; D013058:Mass Spectrometry; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics / Q000379:methods; D011809:Quinones / Q000494:pharmacology; D020365:RNA Helicases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques
D016227:Benzoquinones; D003067:Coenzymes; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018832:Molecular Chaperones; D011809:Quinones; D029701:Saccharomyces cerevisiae Proteins; C571197:Tah1 protein, S cerevisiae; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C428198:RVB1 protein, S cerevisiae; C428199:RVB2 protein, S cerevisiae; D004265:DNA Helicases; D020365:RNA Helicases; C001277:geldanamycin