TY - JOUR
T1 - Navigating the chaperone network
T2 - An integrative map of physical and genetic interactions mediated by the hsp90 chaperone
AU - Zhao, Rongmin
AU - Davey, Mike
AU - Hsu, Ya Chieh
AU - Kaplanek, Pia
AU - Tong, Amy
AU - Parsons, Ainslie B.
AU - Krogan, Nevan
AU - Cagney, Gerard
AU - Mai, Duy
AU - Greenblatt, Jack
AU - Boone, Charles
AU - Emili, Andrew
AU - Houry, Walid A.
N1 - Funding Information:
The authors wish to thank M. Patricia Hernandez, Philip Wong, Alex Ignatchenko, Kyung Seok Dan Im, and Leanne O’Connor for technical assistance. We thank Dr. Jacqueline Segall for careful reading of the manuscript. This work was supported in part by a National Science and Engineering Research Council of Canada grant to A.E., W.A.H., G.C., and C.B., a grant from PENCE to A.E., a grant from the Canadian Institutes of Health Research to C.B., and funds from Genome Canada, the Ontario Genome Institute, and the Ontario Research and Development Challenge Fund to A.E., J.G., and C.B. W.A.H. is a Canadian Institutes of Health Research New Investigator.
PY - 2005/3/11
Y1 - 2005/3/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/20044382800
U2 - 10.1016/j.cell.2004.12.024
DO - 10.1016/j.cell.2004.12.024
M3 - Article
C2 - 15766533
AN - SCOPUS:20044382800
SN - 0092-8674
VL - 120
SP - 715
EP - 727
JO - Cell
JF - Cell
IS - 5
ER -