Ubiquitin Binding by a CUE Domain Regulates Ubiquitin Chain Formation by ERAD E3 Ligases

Katrin Bagola, Maximilian vonDelbrück, Gunnar Dittmar, Martin Scheffner, Inbal Ziv, Michael H. Glickman, Aaron Ciechanover, Thomas Sommer*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

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 andactivator 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 invitro. Mutations that abolish ubiquitin binding by Cue1p affect the turnover of ERAD substrates invivo. 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.

Original languageEnglish
Pages (from-to)528-539
Number of pages12
JournalMolecular Cell
Volume50
Issue number4
DOIs
Publication statusPublished - 23 May 2013
Externally publishedYes

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