title: Mapping the Hsp90 genetic interaction network in Candida albicans reveals environmental contingency and rewired circuitry.
abstract: The molecular chaperone Hsp90 regulates the folding of diverse signal transducers in all eukaryotes, profoundly affecting cellular circuitry. In fungi, Hsp90 influences development, drug resistance, and evolution. Hsp90 interacts with -10% of the proteome in the model yeast Saccharomyces cerevisiae, while only two interactions have been identified in Candida albicans, the leading fungal pathogen of humans. Utilizing a chemical genomic approach, we mapped the C. albicans Hsp90 interaction network under diverse stress conditions. The chaperone network is environmentally contingent, and most of the 226 genetic interactors are important for growth only under specific conditions, suggesting that they operate downstream of Hsp90, as with the MAPK Hog1. Few interactors are important for growth in many environments, and these are poised to operate upstream of Hsp90, as with the protein kinase CK2 and the transcription factor Ahr1. We establish environmental contingency in the first chaperone network of a fungal pathogen, novel effectors upstream and downstream of Hsp90, and network rewiring over evolutionary time.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Diezmann
authors.forename: Magali
authors.initials: M
authors.lastname: Michaut
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Shapiro
authors.forename: Gary D
authors.initials: GD
authors.lastname: Bader
authors.forename: Leah E
authors.initials: LE
authors.lastname: Cowen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D003470:Culture Media; D004783:Environmental Microbiology; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D010770:Phosphotransferases / Q000378:metabolism; D060066:Protein Interaction Maps / Q000187:drug effects / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D016227:Benzoquinones; D003470:Culture Media; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; C001277:geldanamycin