Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor

Cláudia P Grou; Andreia F Carvalho; Manuel P Pinto; Sebastian Wiese; Heike Piechura; Helmut E Meyer; Bettina Warscheid; Clara Sá-Miranda; Jorge E Azevedo

doi:10.1074/jbc.M800402200

Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor

J Biol Chem. 2008 May 23;283(21):14190-7. doi: 10.1074/jbc.M800402200. Epub 2008 Mar 22.

Authors

Cláudia P Grou¹, Andreia F Carvalho, Manuel P Pinto, Sebastian Wiese, Heike Piechura, Helmut E Meyer, Bettina Warscheid, Clara Sá-Miranda, Jorge E Azevedo

Affiliation

¹ Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre, Porto, Portugal.

PMID: 18359941
DOI: 10.1074/jbc.M800402200

Abstract

According to current models of peroxisomal biogenesis, newly synthesized peroxisomal matrix proteins are transported into the organelle by Pex5p. Pex5p recognizes these proteins in the cytosol, mediates their membrane translocation, and is exported back into the cytosol in an ATP-dependent manner. We have previously shown that export of Pex5p is preceded by (and requires) monoubiquitination of a conserved cysteine residue present at its N terminus. In yeasts, and probably also in plants, ubiquitination of Pex5p is mediated by a specialized ubiquitin-conjugating enzyme, Pex4p. In mammals, the identity of this enzyme has remained unknown for many years. Here, we provide evidence suggesting that E2D1/2/3 (UbcH5a/b/c) are the mammalian functional counterparts of yeast/plant Pex4p. The mechanistic implications of these findings are discussed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Cysteine / genetics
Cysteine / metabolism
Cytosol / metabolism
Gene Deletion
Humans
Male
Membrane Transport Proteins / genetics
Membrane Transport Proteins / metabolism*
Peroxisome-Targeting Signal 1 Receptor
Peroxisomes / metabolism*
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Transport
Rats
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Ubiquitin-Conjugating Enzymes / classification
Ubiquitin-Conjugating Enzymes / genetics
Ubiquitin-Conjugating Enzymes / metabolism*
Ubiquitination

Substances

Membrane Transport Proteins
PEX5 protein, S cerevisiae
Peroxisome-Targeting Signal 1 Receptor
Protein Isoforms
Receptors, Cytoplasmic and Nuclear
Recombinant Proteins
Saccharomyces cerevisiae Proteins
Ubiquitin-Conjugating Enzymes
Cysteine