Factors involved in ubiquitination and deubiquitination of PEX5, the peroxisomal shuttling receptor

Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and post-translationally targeted to the organelle by the soluble factor PEX5. Besides a role as a receptor, and probably as a chaperone, PEX5 also holds the key to the matrix of the organelle. Indeed, the available data suggest that PEX5 itself pushes these proteins across the peroxisomal membrane using as driving force the strong protein-protein interactions that it establishes with components of the peroxisomal membrane docking/translocation module (DTM). In recent years, much has been learned on how this transport system is reset and kept fine-tuned. Notably, this involves covalent modification of PEX5 with ubiquitin. Two types of PEX5 ubiquitination have been characterized: monoubiquitination at a conserved cysteine, a mandatory event for the extraction of PEX5 from the DTM; and polyubiquitination, probably the result of a quality control mechanism aiming at clearing the DTM from entangled PEX5 molecules. Monoubiquitination of PEX5 is transient in nature and the factors that reverse this modification have recently been identified. This work was funded by FEDER funds through the Operational Competitiveness Programme — COMPETE and by National Funds through FCT — Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124-FEDER-019731 (PTDC/BIA-BCM/118577/2010). T. A. R., T. F., M. P. P. and C. P. G. are supported by Fundação para a Ciência e a Tecnologia, Programa Operacional Potencial Humano do QREN, and Fundo Social Europeu. A. F. C. is supported by Programa Ciência, funded by Programa Operacional Potencial Humano do QREN, Tipologia 4.2, Promoção do Emprego Científico, by Fundo Social Europeu and by national funds from Ministério da Ciência, Tecnologia e Ensino Superior.