Sts1 can overcome the loss of Rad23 and Rpn10 and represents a novel regulator of the ubiquitin/proteasome pathway.
A rad23Delta rpn10Delta double mutant accumulates multi-Ub proteins, is deficient in proteolysis, and displays sensitivity to drugs that generate damaged proteins. Overexpression of Sts1 restored normal growth in rad23Delta rpn10Delta but did not overcome the DNA repair defect of rad23Delta. To understand the nature of Sts1 suppression, we characterized sts1-2, a temperature-sensitive mutant. We determined that sts1-2 was sensitive to translation inhibitors, accumulated high levels of multi-Ub proteins, and caused stabilization of proteolytic substrates. Additionally, ubiquitinated proteins that were detected in proteasomes were inefficiently cleared in sts1-2. Despite these proteolytic defects, overall proteasome activity was increased in sts1-2. We propose that Sts1 is a new regulatory factor in the ubiquitin/proteasome pathway that controls the turnover of proteasome substrates.
Romero-Perez
Lizbeth
L
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Chen
Li
L
Lambertson
David
D
Madura
Kiran
K
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C490846:RAD23 protein, S cerevisiae; C122019:RPN10 protein, S cerevisiae; C085810:STS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex