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ABSTRACT Proteins enter the secretory pathway through the endoplasmic reticulum1, which delivers properly folded proteins to their site of action2 and contains a quality-control system to
monitor and prevent abnormal proteins from being delivered3. Many of these proteins are degraded by the cytoplasmic proteasome4,5,6,7,8, which requires their retrograde transport to the
cytoplasm5,6. Based on a co-immunoprecipitation of major histocompatibility complex (MHC) class I heavy-chain breakdown intermediates with the translocon subunit Sec61p (refs 9, 10), it was
speculated that Sec61p may be involved in retrograde transport11. Here we present functional evidence from genetic studies that Sec61p mediates retrograde transport of a mutated lumenal
yeast carboxypeptidase ycsY (CPY*) _in vivo_. The endoplasmic reticulum lumenal chaperone BiP (Kar2p) and Sec63p, which are also subunits of the import machinery10,12, are involved in export
of CPY* to the cytosol. Thus our results demonstrate that retrograde transport of proteins is mediated by a functional translocon. We consider the export of endoplasmic reticulum-localized
proteins to the cytosol by the translocon for proteasome degradation to be a general process in eukaryotic cell biology. Access through your institution Buy or subscribe This is a preview of
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PROCESSING DURING ER-ASSOCIATED PROTEIN DEGRADATION Article 01 August 2023 STRUCTURE AND TRANSPORT MECHANISM OF P5B-ATPASES Article Open access 25 June 2021 THE ROLE OF RNF149 IN THE
PRE-EMPTIVE QUALITY CONTROL SUBSTRATE UBIQUITINATION Article Open access 08 April 2023 REFERENCES * Pryer, N. K., Wuestehube, L. J. & Schekman, R. Vesicle-mediated protein sorting.
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homolog of the mammalian BiP/GRP78 gene. _Cell_ 57, 1211–1221 (1989). Google Scholar Download references ACKNOWLEDGEMENTS We thank M. Hochstrasser (Deg1-β-galactosidase fusion), M. D. Rose
(_kar2-113_ allele), T. A. Rapoport (Sec61p antibodies), H. K. Rudolph and R. Schekman (Kar2 antibodies), M. Knop (polyclonal CPY antibodies) and S. Rupp (proteinase yscA antibodies) for
providing gene constructs and affinity purified antibodies; and S. Jäger and M. Hämmerle for discussions. This work was supported by the Bundesministerium für Forschung und Technologie and
the Fonds der Chemischen Industrie, Frankfurt. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institut für Biochemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569, Stuttgart, Germany
Richard K. Plemper, Sigrun Böhmler, Javier Bordallo & Dieter H. Wolf * Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle Strasse 10, D-13122, Berlin, Germany Thomas Sommer
Authors * Richard K. Plemper View author publications You can also search for this author inPubMed Google Scholar * Sigrun Böhmler View author publications You can also search for this
author inPubMed Google Scholar * Javier Bordallo View author publications You can also search for this author inPubMed Google Scholar * Thomas Sommer View author publications You can also
search for this author inPubMed Google Scholar * Dieter H. Wolf View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Plemper, R., Böhmler, S., Bordallo, J. _et al._ Mutant analysis links the translocon and BiP to retrograde protein transport for ER
degradation. _Nature_ 388, 891–895 (1997). https://doi.org/10.1038/42276 Download citation * Received: 14 July 1997 * Accepted: 31 July 1997 * Issue Date: 28 August 1997 * DOI:
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