Department of Biomolecular Chemistry, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Abstract: Yeast strains lacking functional copies of the two genes SSA1 and SSA2, which encode cytosolic molecular chaperones, are temperature-sensitive. In this report, we describe the isolation of a high-copy suppressor of this temperature sensitivity, UBP3, which encodes a de-ubiquitinating enzyme. We show that ubp3 mutant yeast strains have a mild slow-growth phenotype and accumulate ubiquitin-protein conjugates. We propose a model in which Ubp3p acts in vivo to reverse the ubiquitination of substrate proteins, allowing temporarily misfolded proteins an opportunity to fold correctly.