Herp enhances ER-associated protein degradation by recruiting ubiquilins
- Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul 120-749 (Korea, Republic of)
- Department of Biomedical Sciences, The Catholic University of Korea, Seoul 137-040 (Korea, Republic of)
ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3{delta}, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3{delta} was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates.
- OSTI ID:
- 21143659
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 369, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.02.086; PII: S0006-291X(08)00365-3; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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