title: The requirements of yeast Hsp70 of SSA family for the ubiquitin-dependent degradation of short-lived and abnormal proteins.
abstract: Cytoplasmic Hsp70s of SSA family, especially Ssa1p, are involved in the degradation of a variety of misfolded proteins in yeast. However the importance of other Ssa proteins in this process is unclear. To clarify the role(s) of individual Ssa proteins in proteolysis, we measured the breakdown of various cell proteins in mutants lacking different Ssa proteins. In mutants lacking Ssa1p and Ssa2p, the proteasomal degradation of short-lived proteins was reduced, which was not restored fully by the over-expression of Ssa1p. By contrast, the degradation of stable cellular proteins did not require Ssa proteins. The degradation of the cytosolic model substrates (Ub-P-β-gal and R-β-gal) and their ubiquitylation were inhibited by the inactivation of Ssa proteins. In addition, Ssa1p and the co-chaperone Ydj1p are indispensable for the intracellular degradation of a mutant secretory protein, Siiyama variant of human antitrypsin. Our findings indicate that both Ssa1p and Ssa2p are essential for the ubiquitin-dependent degradation of short-lived proteins and the requirements of Ssa proteins and the co-chaperones widely vary depending on the conformations and folding status of the substrates.
authors.affiliation: Department of Bio and Environmental Technology, Seoul Women's University, Seoul, South Korea. Electronic address: do_lee@swu.ac.kr.
authors.forename: Do Hee
authors.initials: do H
authors.lastname: Lee
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Sherman
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address: alfred_goldberg@hms.harvard.edu.
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C542288:SSA2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C070319:YDJ1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae
keywords: Chaperone; Co-chaperone; Degradation; Hsp70; Ubiquitin