%0 Journal Article %1 elmagraouiDeubiquitinationPTS1importReceptor2019 %A El Magraoui, Fouzi %A Brinkmeier, Rebecca %A Mastalski, Thomas %A Hupperich, Alexander %A Strehl, Christofer %A Schwerter, Daniel %A Girzalsky, Wolfgang %A Meyer, Helmut E. %A Warscheid, Bettina %A Erdmann, Ralf %A Platta, Harald W. %C Netherlands %D 2019 %J Biochimica et biophysica acta. Molecular cell research %K 1 Complex/metabolism,Protein Cytoplasmic Deletion/genetics,Signal Deubiquitination,Membrane Endopeptidase Nuclear/metabolism,Saccharomyces Post-Translational,Protein Processing Proteins/genetics/metabolism,Mutation/genetics,Peroxins,Peroxisomal Proteins/metabolism/physiology,Saccharomyces Receptor/genetics/*metabolism/physiology,Peroxisomes,Peroxisomes/*metabolism/physiology,Pex5p,Polyubiquitin/metabolism,Proteasome Signal Signals/*physiology,Peroxisome-Targeting Targeting Transduction,to_read,Ubiquitin,Ubiquitin/metabolism,Ubiquitination/physiology Transport Transport/physiology,Proteolysis,Receptor,Receptors and cerevisiae cerevisiae/metabolism,Sequence transport,Protein %N 2 %P 199--213 %R 10.1016/j.bbamcr.2018.11.002 %T The Deubiquitination of the PTS1-import Receptor Pex5p Is Required for Peroxisomal Matrix Protein Import. %V 1866 %X Peroxisomal biogenesis depends on the correct import of matrix proteins into the lumen of the organelle. Most peroxisomal matrix proteins harbor the peroxisomal targeting-type 1 (PTS1), which is recognized by the soluble PTS1-receptor Pex5p in the cytosol. Pex5p ferries the PTS1-proteins to the peroxisomal membrane and releases them into the lumen. Finally, the PTS1-receptor is monoubiquitinated on the conserved cysteine 6 in Saccharomyces cerevisiae. The monoubiquitinated Pex5p is recognized by the peroxisomal export machinery and is retrotranslocated into the cytosol for further rounds of protein import. However, the functional relevance of deubiquitination has not yet been addressed. In this study, we have analyzed a Pex5p-truncation lacking Cys6 ($\Delta$6)Pex5p, a construct with a ubiquitin-moiety genetically fused to the truncation Ub-($\Delta$6)Pex5p, as well as a construct with a reduced susceptibility to deubiquitination Ub(G75/76A)-($\Delta$6)Pex5p. While the ($\Delta$6)Pex5p-truncation is not functional, the Ub-($\Delta$6)Pex5p chimeric protein can facilitate matrix protein import. In contrast, the Ub(G75/76A)-($\Delta$6)Pex5p chimera exhibits a complete PTS1-import defect. The data show for the first time that not only ubiquitination but also deubiquitination rates are tightly regulated and that efficient deubiquitination of Pex5p is essential for peroxisomal biogenesis.

@article{elmagraouiDeubiquitinationPTS1importReceptor2019, abstract = {Peroxisomal biogenesis depends on the correct import of matrix proteins into the lumen of the organelle. Most peroxisomal matrix proteins harbor the peroxisomal targeting-type 1 (PTS1), which is recognized by the soluble PTS1-receptor Pex5p in the cytosol. Pex5p ferries the PTS1-proteins to the peroxisomal membrane and releases them into the lumen. Finally, the PTS1-receptor is monoubiquitinated on the conserved cysteine 6 in Saccharomyces cerevisiae. The monoubiquitinated Pex5p is recognized by the peroxisomal export machinery and is retrotranslocated into the cytosol for further rounds of protein import. However, the functional relevance of deubiquitination has not yet been addressed. In this study, we have analyzed a Pex5p-truncation lacking Cys6 [({$\Delta$}6)Pex5p], a construct with a ubiquitin-moiety genetically fused to the truncation [Ub-({$\Delta$}6)Pex5p], as well as a construct with a reduced susceptibility to deubiquitination [Ub(G75/76A)-({$\Delta$}6)Pex5p]. While the ({$\Delta$}6)Pex5p-truncation is not functional, the Ub-({$\Delta$}6)Pex5p chimeric protein can facilitate matrix protein import. In contrast, the Ub(G75/76A)-({$\Delta$}6)Pex5p chimera exhibits a complete PTS1-import defect. The data show for the first time that not only ubiquitination but also deubiquitination rates are tightly regulated and that efficient deubiquitination of Pex5p is essential for peroxisomal biogenesis.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {Netherlands}, author = {El Magraoui, Fouzi and Brinkmeier, Rebecca and Mastalski, Thomas and Hupperich, Alexander and Strehl, Christofer and Schwerter, Daniel and Girzalsky, Wolfgang and Meyer, Helmut E. and Warscheid, Bettina and Erdmann, Ralf and Platta, Harald W.}, biburl = {https://www.bibsonomy.org/bibtex/2464efd94a272384a6685ecd426fe9bdb/warscheidlab}, copyright = {Copyright {\copyright} 2018 Elsevier B.V. All rights reserved.}, doi = {10.1016/j.bbamcr.2018.11.002}, interhash = {95f6961152c40f2b5b03a1bd1622bf02}, intrahash = {464efd94a272384a6685ecd426fe9bdb}, issn = {1879-2596 0167-4889}, journal = {Biochimica et biophysica acta. Molecular cell research}, keywords = {1 Complex/metabolism,Protein Cytoplasmic Deletion/genetics,Signal Deubiquitination,Membrane Endopeptidase Nuclear/metabolism,Saccharomyces Post-Translational,Protein Processing Proteins/genetics/metabolism,Mutation/genetics,Peroxins,Peroxisomal Proteins/metabolism/physiology,Saccharomyces Receptor/genetics/*metabolism/physiology,Peroxisomes,Peroxisomes/*metabolism/physiology,Pex5p,Polyubiquitin/metabolism,Proteasome Signal Signals/*physiology,Peroxisome-Targeting Targeting Transduction,to_read,Ubiquitin,Ubiquitin/metabolism,Ubiquitination/physiology Transport Transport/physiology,Proteolysis,Receptor,Receptors and cerevisiae cerevisiae/metabolism,Sequence transport,Protein}, langid = {english}, month = feb, number = 2, pages = {199--213}, pmid = {30408545}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {The Deubiquitination of the {{PTS1-import}} Receptor {{Pex5p}} Is Required for Peroxisomal Matrix Protein Import.}, volume = 1866, year = 2019 }