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Originally published In Press as doi:10.1074/jbc.M403632200 on November 9, 2004

J. Biol. Chem., Vol. 280, Issue 3, 1921-1930, January 21, 2005
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Ubiquitination of the Peroxisomal Targeting Signal Type 1 Receptor, Pex5p, Suggests the Presence of a Quality Control Mechanism during Peroxisomal Matrix Protein Import*

Jan A. K. W. Kiel{ddagger}§, Kerstin Emmrich{ddagger}, Helmut E. Meyer||, and Wolf-H. Kunau{ddagger}

From the {ddagger}Abteilung für Zellbiochemie and the ||Medical Proteom Center, Medizinische Fakultät der Ruhr-Universität Bochum, D-44780 Bochum, Germany

PEX genes encode proteins (peroxins) that are required for the biogenesis of peroxisomes. One of these peroxins, Pex5p, is the receptor for matrix proteins with a type 1 peroxisomal targeting signal (PTS1), which shuttles newly synthesized proteins from the cytosol into the peroxisome matrix. We observed that in various Saccharomyces cerevisiae pex mutants disturbed in the early stages of PTS1 import, the steady-state levels of Pex5p are enhanced relative to wild type controls. Furthermore, we identified ubiquitinated forms of Pex5p in deletion mutants of those PEX genes that have been implicated in recycling of Pex5p from the peroxisomal membrane into the cytosol. Pex5p ubiquitination required the presence of the ubiquitin-conjugating enzyme Ubc4p and the peroxins that are required during early stages of PTS1 protein import. Finally, we provide evidence that the proteasome is involved in the turnover of Pex5p in wild type yeast cells, a process that requires Ubc4p and occurs at the peroxisomal membrane. Our data suggest that during receptor recycling a portion of Pex5p becomes ubiquitinated and degraded by the proteasome. We propose that this process represents a conserved quality control mechanism in peroxisome biogenesis.


Received for publication, April 1, 2004 , and in revised form, October 27, 2004.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the Sonderforschungsbereiche (Grant SFB480/Teil-projekt B1) and by the Deutsche Forschungs Gemeinschaft (DFG Grant Ku 329/17-5).

§ Supported by the Sonderforschungsbereiche (Grants SFB394 and SFB480). To whom correspondence should be addressed (present address): Eukaryotic Microbiology, GBB, University of Groningen, Kerklaan 30 NL-9751 NN Haren, The Netherlands. Tel.: 31-50-363-2218; Fax: 31-50-363-2154; E-mail: J.A.K.W.Kiel{at}Biol.RUG.nl.


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