Herp enhances ER-associated protein degradation by recruiting ubiquilins

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

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)


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
Issue number2
Publication statusPublished - 2008 May 2

Bibliographical note

Funding Information:
This work was supported in part by grants from the Korean Ministry of Science and Technology through Studies on Ubiquitome Functions Project and from the Korea Science and Engineering Foundation through Protein Network Research Center at Yonsei University.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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