Isolation of UBP3, encoding a de-ubiquitinating enzyme, as a multicopy suppressor of a heat-shock mutant strain of S-cerevisiae

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.