Identification of SSF1, CNS1, and HCH1 as multicopy suppressors of a Saccharomyces cerevisiae Hsp90 loss-of-function mutation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 4; pp. 1409 - 1414
• Main Authors: Nathan, D.F. (Cadus Pharmaceutical Corp., Tarrytown, NY.), Vos, M.H, Lindquist, S
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 16.02.1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: ALLELE-SPECIFIC SUPPRESSORS; ALLELES; Amino Acid Substitution; Amino acids; BINDING PROTEINS; Biological Sciences; Cell biology; Cell growth; Cells; Cellular biology; Chromosome Mapping; Chromosomes, Fungal; FENOTIPOS; Fungal Proteins - genetics; Fungal Proteins - metabolism; GENE; GENES; Genes, Essential; Genes, Fungal; Genes, Suppressor; Genetic mutation; Genetic screening; HEAT SHOCK PROTEINS; HSP90 Heat-Shock Proteins - genetics; INHIBITOR GENES; INTERACTIONS; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Multigene Family; MUTACION; Mutagenesis; MUTANT; MUTANTES; MUTANTS; MUTATION; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncogene Protein pp60(v-src) - genetics; Oncogene Protein pp60(v-src) - metabolism; Open Reading Frames; PHENOTYPE; PHENOTYPES; Plasmids; PROTEINAS AGLUTINANTES; PROTEINAS DE SHOCK TERMICO; PROTEINE DE CHOC THERMIQUE; PROTEINE DE LIAISON; Proteins; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins; Temperature; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.4.1409

Hsp90 functions in a multicomponent chaperone system to promote the maturation and maintenance of a diverse, but specific, set of target proteins that play key roles in the regulation of cell growth and development. To identify additional components of the Hsp90 chaperone system and its targets, we searched for multicopy suppressors of various temperature-sensitive mutations in the yeast Hsp90 gene, HSP82. Three suppressors were isolated for one Hsp90 mutant (glutamate leads to lysine at amino acid 381). Each exhibited a unique, allele-specific pattern of suppression with other Hsp90 mutants and had unique structural and biological properties. SSF1 is a member of an essential gene family and functions in the response to mating pheromones. CNS1 is an essential gene that encodes a component of the Hsp90 chaperone machinery. The role of HCH1 is unknown; its sequence has no strong homology to any protein of known function. SSF1 and CNS1 were weak suppressors, whereas HCH1 restored wild-type growth rates at all temperatures tested to cells expressing the E381K mutant. Overexpression of CNS1 or HCH1, but not SSF1, enhanced the maturation of a heterologous Hsp90 target protein, p60(v-src). These results suggest that like Cns1p, Hch1p is a general modulator of Hsp90 chaperone functions, whereas Ssf1p likely is either an Hsp90 target protein or functions in the same pathway as an Hsp90 target protein