Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor.
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.
Grou
Cláudia P
CP
Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre, Porto, Portugal.
Carvalho
Andreia F
AF
Pinto
Manuel P
MP
Wiese
Sebastian
S
Piechura
Heike
H
Meyer
Helmut E
HE
Warscheid
Bettina
B
Sá-Miranda
Clara
C
Azevedo
Jorge E
JE
D000818:Animals; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D026901:Membrane Transport Proteins; C499509:PEX5 protein, S cerevisiae; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D003545:Cysteine