Mutants of the deubiquitinating enzyme Ubp14 decipher pathway diversity of ubiquitin-proteasome linked protein degradation.
Selective proteolysis is an important regulatory mechanism in all cells. In eukaryotes, this process gains specificity by tagging proteins with the small protein ubiquitin. K48 linked polyubiquitin chains of four and more ubiquitin moieties target proteins for hydrolysis by the proteasome. Prior to degradation the polyubiquitin chain is removed from the protein, cleaved into single units, and recycled. The deubiquitinating enzyme Ubp14 is an important catalyst of this process. Mutants of Ubp14 had been shown to accumulate non-cleaved oligo- and polyubiquitin chains, which resulted in inhibition of overall ubiquitin-proteasome linked proteolysis as well as in inhibition of degradation of some known substrates. Here we show that accumulation of ubiquitin chains due to defective Ubp14 does not uniformly lead to inhibition of ubiquitin-proteasome linked protein degradation. Instead, inhibition of degradation depends on the substrate tested. The results indicate the existence of different paths through which proteins enter the proteasome.
Eisele
Frederik
F
Institut für Biochemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
Braun
Bernhard
B
Pfirrmann
Thorsten
T
Wolf
Dieter H
DH
D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism; D043402:Cathepsin A; D010450:Endopeptidases / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D006597:Fructose-Bisphosphatase; D002268:Carboxypeptidases; D010450:Endopeptidases; D043402:Cathepsin A; C499283:PRC1 protein, S cerevisiae; D046988:Proteasome Endopeptidase Complex; C108364:UBP14 protein, S cerevisiae