title: Ubiquilin interacts with ubiquitylated proteins and proteasome through its ubiquitin-associated and ubiquitin-like domains.
abstract: Mammalian cells acquire tolerance against multiple stressors through the high-level expression of stress-responsible genes. We have previously demonstrated that protein-disulfide isomerase (PDI) together with ubiquilin are up-regulated in response to hypoxia/brain ischemia, and play critical roles in resistance to these damages. We show here that ubiquilin interacts preferentially with poly-ubiquitin chains and 19S proteasome subunits. Taken together, these results suggest that ubiquitin could serve as an adaptor protein that both interacts with PDI and mediates the delivery of poly-ubiquitylated proteins to the proteasome in the cytosol in the vicinity of the endoplasmic reticulum membrane.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Han Seok
authors.initials: HS
authors.lastname: Ko
authors.forename: Takashi
authors.initials: T
authors.lastname: Uehara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; C122019:RPN10 protein, S cerevisiae; D011994:Recombinant Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C107792:UBQLN1 protein, human; D025801:Ubiquitin; D025821:Polyubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex