title: Ubiquitination of the peroxisomal targeting signal type 1 receptor, Pex5p, suggests the presence of a quality control mechanism during peroxisomal matrix protein import.
abstract: 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.
authors.affiliation: Abteilung für Zellbiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, Germany. J.A.K.W.Kiel@Biol.RUG.nl
authors.forename: Jan A K W
authors.initials: JA
authors.lastname: Kiel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Emmrich
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Wolf-H
authors.initials: WH
authors.lastname: Kunau
mesh_terms: D005656:Fungal Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D026901:Membrane Transport Proteins; C499509:PEX5 protein, S cerevisiae; D000074435:Peroxisome-Targeting Signal 1 Receptor; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin