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The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev Cell 2003 Nov;5(5):709-22

Date

11/07/2003

Pubmed ID

14602072

DOI

10.1016/s1534-5807(03)00321-6

Scopus ID

2-s2.0-0242362743   295 Citations

Abstract

Ubiquitination of the chemokine receptor CXCR4 serves as a targeting signal for lysosomal degradation, but the mechanisms mediating ubiquitination and lysosomal sorting remain poorly understood. Here we report that the Nedd4-like E3 ubiquitin ligase AIP4 mediates ubiquitination of CXCR4 at the plasma membrane, and of the ubiquitin binding protein Hrs on endosomes. CXCR4 activation promotes CXCR4 colocalization with AIP4 and Hrs within the same region of endosomes. Endosomal sorting of CXCR4 is dependent on Hrs as well as the AAA ATPase Vps4, the latter involved in regulating the ubiquitination status of both CXCR4 and Hrs. We propose a model whereby AIP4, Hrs, and Vps4 coordinate a cascade of ubiquitination and deubiquitination events that sort CXCR4 to the degradative pathway.

Author List

Marchese A, Raiborg C, Santini F, Keen JH, Stenmark H, Benovic JL

Author

Adriano Marchese PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphatases
Animals
Cell Line
Cell Membrane
Endocytosis
Endosomal Sorting Complexes Required for Transport
Endosomes
Humans
Immunohistochemistry
Lysosomes
Molecular Sequence Data
Phosphoproteins
Protein Transport
Receptors, CXCR4
Repressor Proteins
Saccharomyces cerevisiae Proteins
Ubiquitin
Ubiquitin-Protein Ligases