title: Pex2 and pex12 function as protein-ubiquitin ligases in peroxisomal protein import.
abstract: The PTS1-dependent peroxisomal matrix protein import is facilitated by the receptor protein Pex5 and can be divided into cargo recognition in the cytosol, membrane docking of the cargo-receptor complex, cargo release, and recycling of the receptor. The final step is controlled by the ubiquitination status of Pex5. While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle. Recently, the ubiquitin-conjugating enzymes involved in Pex5 ubiquitination were identified as Ubc4 and Pex4 (Ubc10), whereas the identity of the corresponding protein-ubiquitin ligases remained unknown. Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.
authors.affiliation: Institut für Physiologische Chemie, Ruhr-Universität Bochum, Universitätsstr. 150, D-44780 Bochum, Germany.
authors.forename: Harald W
authors.initials: HW
authors.lastname: Platta
authors.forename: Fouzi
authors.initials: F
authors.lastname: El Magraoui
authors.forename: Bastian E
authors.initials: BE
authors.lastname: Bäumer
authors.forename: Daniel
authors.initials: D
authors.lastname: Schlee
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Girzalsky
authors.forename: Ralf
authors.initials: R
authors.lastname: Erdmann
mesh_terms: D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D000074401:Peroxins; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000201:enzymology*; D021381:Protein Transport / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C491335:PEX12 protein, S cerevisiae; C499509:PEX5 protein, S cerevisiae; D000074401:Peroxins; D000074435:Peroxisome-Targeting Signal 1 Receptor; C114542:RFX1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C501306:Ubc4 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; C544541:Pex2 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases
references.citation: EMBO J. 1999 Dec 1;18(23):6832-44
references.pmid: 10581257
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11364-9
references.pmid: 10500182
references.citation: Cell. 1997 Apr 4;89(1):83-92
references.pmid: 9094717
references.citation: Cell. 1991 Feb 8;64(3):483-4
references.pmid: 1991318
references.citation: Biol Chem. 2007 Nov;388(11):1209-14
references.pmid: 17976014
references.citation: J Cell Biol. 2007 Apr 23;177(2):197-204
references.pmid: 17452527
references.citation: Yeast. 1999 Jul;15(10B):963-72
references.pmid: 10407276
references.citation: FEBS Lett. 1992 Nov 2;312(1):1-2
references.pmid: 1426230
references.citation: Nat Rev Mol Cell Biol. 2005 Sep;6(9):738-42
references.pmid: 16103872
references.citation: J Biol Chem. 2005 Mar 4;280(9):7867-74
references.pmid: 15632140
references.citation: J Biol Chem. 2007 Aug 3;282(31):22534-43
references.pmid: 17550898
references.citation: Cell. 1991 Feb 8;64(3):499-510
references.pmid: 1825027
references.citation: Exp Cell Res. 2001 Feb 1;263(1):98-106
references.pmid: 11161709
references.citation: J Cell Biol. 1996 Dec;135(6 Pt 2):1763-74
references.pmid: 8991089
references.citation: J Cell Biol. 1999 Nov 15;147(4):761-74
references.pmid: 10562279
references.citation: Histochem Cell Biol. 2008 Apr;129(4):421-40
references.pmid: 18274771
references.citation: Nature. 1992 Sep 3;359(6390):73-6
references.pmid: 1326082
references.citation: Biochem J. 2004 Nov 15;384(Pt 1):37-45
references.pmid: 15283676
references.citation: J Biol Chem. 2008 May 23;283(21):14190-7
references.pmid: 18359941
references.citation: Mol Biol Cell. 2006 Feb;17(2):690-9
references.pmid: 16319171
references.citation: J Cell Biol. 1999 Mar 22;144(6):1151-62
references.pmid: 10087260
references.citation: Cell. 2000 Aug 18;102(4):533-9
references.pmid: 10966114
references.citation: J Biol Chem. 2005 Jan 7;280(1):515-24
references.pmid: 15509568
references.citation: J Cell Biol. 2006 Jan 2;172(1):67-78
references.pmid: 16390998
references.citation: Nat Struct Mol Biol. 2007 Oct;14(10):941-8
references.pmid: 17873885
references.citation: Mol Cell Biol. 2005 Dec;25(24):10822-32
references.pmid: 16314507
references.citation: PLoS One. 2008 Jan 23;3(1):e1487
references.pmid: 18213395
references.citation: Genetics. 2005 Dec;171(4):1477-84
references.pmid: 16118187
references.citation: Biochim Biophys Acta. 2006 Dec;1763(12):1733-48
references.pmid: 17055079
references.citation: Biochem Biophys Res Commun. 2008 Oct 3;374(4):620-4
references.pmid: 18644345
references.citation: EMBO J. 1994 Oct 17;13(20):4908-18
references.pmid: 7957058
references.citation: Traffic. 2002 Aug;3(8):560-74
references.pmid: 12121419
references.citation: Nat Rev Mol Cell Biol. 2005 Aug;6(8):610-21
references.pmid: 16064137
references.citation: Annu Rev Cell Dev Biol. 2006;22:159-80
references.pmid: 16753028
references.citation: Plant Physiol. 2003 Dec;133(4):1991-9
references.pmid: 14630959
references.citation: Nat Cell Biol. 2001 Jan;3(1):24-9
references.pmid: 11146622
references.citation: Genes Dev. 2001 Oct 15;15(20):2660-74
references.pmid: 11641273
references.citation: Proteins. 2004 Feb 15;54(3):455-67
references.pmid: 14747994
references.citation: Proc Natl Acad Sci U S A. 1958 Feb;44(2):162-6
references.pmid: 16590160
references.citation: Nucleic Acids Res. 1996 Jul 1;24(13):2519-24
references.pmid: 8692690
references.citation: Nature. 1991 Mar 7;350(6313):77-81
references.pmid: 1750930
references.citation: Nat Cell Biol. 2005 Aug;7(8):817-22
references.pmid: 16007078
references.citation: Mol Cell. 2003 Mar;11(3):635-46
references.pmid: 12667447
references.citation: Science. 1992 Feb 28;255(5048):1132-4
references.pmid: 1546315
references.citation: FEBS J. 2006 Aug;273(16):3804-15
references.pmid: 16911527
references.citation: J Biol Chem. 2007 Oct 26;282(43):31267-72
references.pmid: 17726030
references.citation: Biochim Biophys Acta. 2006 Dec;1763(12):1552-64
references.pmid: 17011644
references.citation: J Biol Chem. 2006 Sep 15;281(37):27003-15
references.pmid: 16849337
references.citation: EMBO J. 2000 Jan 17;19(2):223-33
references.pmid: 10637226
references.citation: Eur J Cell Biol. 2001 Apr;80(4):257-70
references.pmid: 11370741
references.citation: J Biol Chem. 2005 Jan 21;280(3):1921-30
references.pmid: 15536088