TY - JOUR
T1 - Ubiquitin Binding by a CUE Domain Regulates Ubiquitin Chain Formation by ERAD E3 Ligases
AU - Bagola, Katrin
AU - vonDelbrück, Maximilian
AU - Dittmar, Gunnar
AU - Scheffner, Martin
AU - Ziv, Inbal
AU - Glickman, Michael H.
AU - Ciechanover, Aaron
AU - Sommer, Thomas
N1 - Funding Information:
The authors wish to thank the members of their research groups for discussions, unpublished data, and materials. The Deutsche Forschungsgemeinschaft generously supports research in the laboratory of T.S. (SFB 740, Priority Program 1365). T.S., A.C., and M.H.G. receive joined funding from the German-Israel Project Cooperation DIP. A.C. acknowledges the support of the AMRF (Adelson Medical Research Foundation) and an ICRF (Israel Cancer Research Fund) Professorship.
PY - 2013/5/23
Y1 - 2013/5/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878209042&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2013.04.005
DO - 10.1016/j.molcel.2013.04.005
M3 - Article
C2 - 23665229
AN - SCOPUS:84878209042
SN - 1097-2765
VL - 50
SP - 528
EP - 539
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -