title: Hsp90 Maintains Proteostasis of the Galactose Utilization Pathway To Prevent Cell Lethality.
abstract: Hsp90 is a molecular chaperone that aids in the folding of its metastable client proteins. Past studies have shown that it can exert a strong impact on some cellular pathways by controlling key regulators. However, it is unknown whether several components of a single pathway are collectively regulated by Hsp90. Here, we observe that Hsp90 influences the protein abundance of multiple Gal proteins and the efficiency of galactose utilization even after the galactose utilization pathway (GAL pathway) is fully induced. The effect of Hsp90 on Gal proteins is not at the transcriptional level. Moreover, Gal1 is found to physically interact with Hsp90, and its stability is reduced in low-Hsp90 cells. When Hsp90 is compromised, several Gal proteins form protein aggregates that colocalize with the disaggregase Hsp104. These results suggest that Gal1 and other Gal proteins are probably the clients of Hsp90. An unbalanced GAL pathway has been known to cause fatal growth arrest due to accumulation of toxic galactose metabolic intermediates. It is likely that Hsp90 chaperones multiple Gal proteins to maintain proteostasis and prevent cell lethality especially in a fluctuating environment.
authors.affiliation: Molecular and Cell Biology, Taiwan International Graduate Program, Graduate Institute of Life Sciences, National Defense Medical Center, and Academia Sinica, Taipei, Taiwan Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Rajaneesh Karimpurath
authors.initials: RK
authors.lastname: Gopinath
authors.affiliation: Molecular and Cell Biology, Taiwan International Graduate Program, Graduate Institute of Life Sciences, National Defense Medical Center, and Academia Sinica, Taipei, Taiwan jleu@imb.sinica.edu.tw.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Leu
mesh_terms: D005686:Galactokinase / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055550:Protein Stability; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase; D005690:Galactose