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Ubiquitin binding by a CUE domain regulates ubiquitin chain formation by ERAD E3 ligases

Official URL:https://doi.org/10.1016/j.molcel.2013.04.005
PubMed:View item in PubMed
Creators Name:Bagola, K. and von Delbrueck, M. and Dittmar, G. and Scheffner, M. and Ziv, I. and Glickman, M.H. and Ciechanover, A. and Sommer, T.
Journal Title:Molecular Cell
Journal Abbreviation:Mol Cell
Page Range:528-539
Date:23 May 2013
Keywords:Amino Acid Sequence, Amino Acid Sequence Homology, Binding Sites, Carrier Proteins, Endoplasmic Reticulum, Lysine, Membrane Proteins, Molecular Sequence Data, Mutation, Polyacrylamide Gel Electrophoresis, Polyubiquitin, Saccharomyces cerevisiae Proteins, Tertiary Protein Structure, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination
Abstract:Ubiquitin-binding domains (UBDs) differentially recognize ubiquitin (ub) modifications. Some of them specifically bind mono-ub, as has been shown for the CUE domain. Interestingly, so far no significant ubiquitin binding has been observed for the CUE domain of yeast Cue1p. Cue1p is receptor and activator of the ubiquitin-conjugating enzyme Ubc7p. It integrates Ubc7p into endoplasmic reticulum (ER) membrane-bound ubiquitin ligase complexes, and thus, it is crucial for ER-associated protein degradation (ERAD). Here we show that the CUE domain of Cue1p binds ubiquitin chains, which is pivotal for the efficient formation of K48-linked polyubiquitin chains in vitro. Mutations that abolish ubiquitin binding by Cue1p affect the turnover of ERAD substrates in vivo. Our data strongly imply that the CUE domain facilitates substrate ubiquitylation by stabilizing growing ubiquitin chains at the ERAD ubiquitin ligases. Hence, we demonstrate an unexpected function of a UBD in the regulation of ubiquitin chain synthesis.
Publisher:Cell Press (U.S.A.)
Item Type:Article

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