Article
- The EMBO Journal (2004) 23, 2206 - 2215
- doi:10.1038/sj.emboj.7600232
Published online: 20 May 2004
Subject Categories:
Uncoupling retro-translocation and degradation in the ER-associated degradation of a soluble protein
Robert J Lee1, Chang-wei Liu2, Carol Harty3, Ardythe A McCracken4, Martin Latterich5, Karin Römisch3, George N DeMartino2, Philip J Thomas2 and Jeffrey L Brodsky1
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- University of Cambridge, Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Cambridge, UK
- Department of Biology, University of Nevada, Reno, Nevada, USA
- Department of Anatomy and Cell Biology, McGill University, Montreal, Canada
Correspondence to:
Jeffrey L Brodsky, Department of Biological Sciences, University of Pittsburgh, 274 Crawford Hall, Pittsburgh, PA 15260, USA. Tel.: +1 412 624 4831; Fax: +1 412 624 4759; E-mail: jbrodsky@pitt.edu
Received 8 January 2004; Accepted 19 April 2004
Abstract
Aberrant polypeptides in the endoplasmic reticulum (ER) are retro-translocated to the cytoplasm and degraded by the 26S proteasome via ER-associated degradation (ERAD). To begin to resolve the requirements for the retro-translocation and degradation steps during ERAD, a cell-free assay was used to investigate the contributions of specific factors in the yeast cytosol and in ER-derived microsomes during the ERAD of a model, soluble polypeptide. As ERAD was unaffected when cytoplasmic chaperone activity was compromised, we asked whether proteasomes on their own supported both export and degradation in this system. Proficient ERAD was observed if wild-type cytosol was substituted with either purified yeast or mammalian proteasomes. Moreover, addition of only the 19S cap of the proteasome catalyzed ATP-dependent export of the polypeptide substrate, which was degraded upon subsequent addition of the 20S particle.
Keywords:
- chaperone,
- endoplasmic reticulum,
- ERAD,
- proteasome,
- retro-translocation
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