In the present study, the human TEB4 is identified as a novel ER (endoplasmic reticulum)-resident ubiquitin ligase. TEB4 has homologues in many species and has a number of remarkable properties. TEB4 contains a conserved RING (really interesting new gene) finger and 13 predicted transmembrane domains. The RING finger of TEB4 and its homologues is situated at the N-terminus and has the unconventional C4HC3 configuration. The N-terminus of TEB4 is located in the cytosol. We show that the isolated TEB4 RING domain catalyses ubiquitin ligation in vitro in a reaction that is ubiquitin Lys48-specific and involves UBC7 (ubiquitin-conjugating enzyme 7). These properties are reminiscent of E3 enzymes, which are involved in ER-associated protein degradation. TEB4 is an ER degradation substrate itself, promoting its own degradation in a RING finger- and proteasome-dependent manner.
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Research Article|
May 24 2005
TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum
Gerco HASSINK;
Gerco HASSINK
*Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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Marjolein KIKKERT;
Marjolein KIKKERT
*Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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Sjaak van VOORDEN;
Sjaak van VOORDEN
*Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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Shiow-Ju LEE;
Shiow-Ju LEE
†Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 161, Sect. 6, Minchiuan E. Road, Neihu Chiu, Taipei 114, Taiwan, Republic of China
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Robbert SPAAPEN;
Robbert SPAAPEN
*Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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Theo van LAAR;
Theo van LAAR
‡Division of Molecular Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
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Catherine S. COLEMAN;
Catherine S. COLEMAN
§Department of Cellular and Molecular Physiology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, U.S.A.
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Eric BARTEE;
Eric BARTEE
∥Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, U.S.A.
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Klaus FRÜH;
Klaus FRÜH
∥Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, U.S.A.
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Vincent CHAU;
Vincent CHAU
§Department of Cellular and Molecular Physiology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, U.S.A.
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Emmanuel WIERTZ
Emmanuel WIERTZ
1
*Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
July 22 2004
Revision Received:
December 23 2004
Accepted:
January 27 2005
Accepted Manuscript online:
January 27 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 388 (2): 647–655.
Article history
Received:
July 22 2004
Revision Received:
December 23 2004
Accepted:
January 27 2005
Accepted Manuscript online:
January 27 2005
Citation
Gerco HASSINK, Marjolein KIKKERT, Sjaak van VOORDEN, Shiow-Ju LEE, Robbert SPAAPEN, Theo van LAAR, Catherine S. COLEMAN, Eric BARTEE, Klaus FRÜH, Vincent CHAU, Emmanuel WIERTZ; TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum. Biochem J 1 June 2005; 388 (2): 647–655. doi: https://doi.org/10.1042/BJ20041241
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