Herp enhances ER-associated protein degradation by recruiting ubiquilins
Abstract
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.
- Authors:
-
- 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)
- Publication Date:
- OSTI Identifier:
- 21143659
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 369; Journal 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); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; GENE REGULATION; MASS SPECTROSCOPY; MEMBRANE PROTEINS; MUTANTS; QUALITY CONTROL; RABBIT TUBES; RNA; SUBSTRATES
Citation Formats
Kim, Tae-Yeon, Kim, Eunmin, Yoon, Sungjoo Kim, and Yoon, Jong-Bok. Herp enhances ER-associated protein degradation by recruiting ubiquilins. United States: N. p., 2008.
Web. doi:10.1016/j.bbrc.2008.02.086.
Kim, Tae-Yeon, Kim, Eunmin, Yoon, Sungjoo Kim, & Yoon, Jong-Bok. Herp enhances ER-associated protein degradation by recruiting ubiquilins. United States. https://doi.org/10.1016/j.bbrc.2008.02.086
Kim, Tae-Yeon, Kim, Eunmin, Yoon, Sungjoo Kim, and Yoon, Jong-Bok. 2008.
"Herp enhances ER-associated protein degradation by recruiting ubiquilins". United States. https://doi.org/10.1016/j.bbrc.2008.02.086.
@article{osti_21143659,
title = {Herp enhances ER-associated protein degradation by recruiting ubiquilins},
author = {Kim, Tae-Yeon and Kim, Eunmin and Yoon, Sungjoo Kim and Yoon, Jong-Bok},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2008.02.086},
url = {https://www.osti.gov/biblio/21143659},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 369,
place = {United States},
year = {Fri May 02 00:00:00 EDT 2008},
month = {Fri May 02 00:00:00 EDT 2008}
}