ISOLATION OF UBP3, ENCODING A DE-UBIQUITINATING ENZYME, AS A MULTICOPY SUPPRESSOR OF A HEAT-SHOCK MUTANT STRAIN OF SACCHAROMYCES-CEREVISIAE

Yeast strains lacking functional copies of the two genes SSA1 and SSA2 , which encode cytosolic molecular chaperones, are temperature-sensiti ve. In this report, we describe the isolation of a high-copy suppresso r of this temperature sensitivity, UBP3, which encodes a de-ubiquitina ting enzyme. We show that ubp3 mutant yeast strains have a mild slow-g rowth phenotype and accumulate ubiquitin-protein conjugates. We propos e a model in which Ubp3p acts in vivo to reverse the ubiquitination of substrate proteins, allowing temporarily misfolded proteins an opport unity to fold correctly.