Herp enhances ER-associated protein degradation by recruiting ubiquilins

Tae Yeon Kim, Eunmin Kim, Sungjoo Kim Yoon, Jong-Bok Yoon

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 CD3δ, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3δ 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.

Original languageEnglish
Pages (from-to)741-746
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume369
Issue number2
DOIs
Publication statusPublished - 2008 May 2

Fingerprint

Proteolysis
Degradation
Proteins
Proteasome Endopeptidase Complex
Substrates
Quality Control
Small Interfering RNA
Membrane Proteins
Membranes
Quality control
Control systems

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Kim, Tae Yeon ; Kim, Eunmin ; Yoon, Sungjoo Kim ; Yoon, Jong-Bok. / Herp enhances ER-associated protein degradation by recruiting ubiquilins. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 369, No. 2. pp. 741-746.
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Herp enhances ER-associated protein degradation by recruiting ubiquilins. / Kim, Tae Yeon; Kim, Eunmin; Yoon, Sungjoo Kim; Yoon, Jong-Bok.

In: Biochemical and Biophysical Research Communications, Vol. 369, No. 2, 02.05.2008, p. 741-746.

Research output: Contribution to journalArticle

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