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PMID: 14988731 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins.

The EMBO journal ·Vol. 23 ·No. 6 ·2004-03-24 ·Pages 1279-88

Hettema EH, Valdez-Taubas J, Pelham HR

Abstract

Membrane proteins destined for the vacuolar or lysosomal lumen are typically ubiquitinated, the ubiquitin serving as a targeting signal for the multivesicular body pathway. The RING-domain ubiquitin ligase Tul1 is an integral membrane protein that modifies the yeast vacuolar enzyme carboxypeptidase S (Cps1), the polyphosphatase Ppn1/Phm5 and other proteins containing exposed hydrophilic residues within their transmembrane domains (TMDs). Here we show that Bsd2 provides an alternative ubiquitination mechanism for Cps1, Phm5 and other proteins. Bsd2 is a three-TMD protein with a PPXY motif that binds the HECT domain ubiquitin ligase Rsp5. It can thus act as a specific adaptor linking Rsp5 to its substrates. Like Tul1, the Bsd2 system recognises polar TMDs. Bsd2 also controls the vacuolar targeting of a manganese transporter and a mutant plasma membrane ATPase, and together with the ER retrieval receptor Rer1, it protects cells from stress. We suggest that Bsd2 has a wide role in the quality control of membrane proteins. Bsd2 is the yeast homologue of human NEDD4 binding protein N4WBP5, which may therefore have similar functions.

MeSH Terms
Amino Acid Sequence Carboxypeptidases/chemistry,metabolism Endosomal Sorting Complexes Required for Transport Gene Expression Regulation, Fungal Ion Transport Membrane Proteins/metabolism Metals/metabolism Molecular Sequence Data Mutation/genetics Protein Binding Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Ubiquitin/metabolism Ubiquitin-Protein Ligase Complexes/genetics,metabolism
Chemicals
BSD2 protein, S cerevisiae Endosomal Sorting Complexes Required for Transport Membrane Proteins Metals Saccharomyces cerevisiae Proteins Ubiquitin Ubiquitin-Protein Ligase Complexes Carboxypeptidases CPS1 protein, S cerevisiae RSP5 protein, S cerevisiae
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hettema Ewald H
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Valdez-Taubas Javier
Pelham Hugh R B
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600137
Published
2004-03-24
Epub
2004-00-26
Pages
1279-88
Language
English
Region
England
NLM ID
8208664
PMCID
PMC381411
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600137 PMC Full Text View journal details
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