ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans.

Abstract

Ataxin-3 is the protein involved in Machado-Joseph disease, a neurodegenerative disorder caused by a polyglutamine expansion. Ataxin-3 binds ubiquitylated proteins and acts as a deubiquitylating enzyme in vitro. It was previously proposed that ataxin-3, along with the VCP/p97 protein, escorts ubiquitylated substrates for proteasomal degradation, although other players of this escort complex were not identified yet. In this work, we show that the Caenorhabditis elegans ataxin-3 protein (ATX-3) interacts with both VCP/p97 worm homologs, CDC-48.1 and CDC-48.2 and we map the interaction domains. We describe a motility defect in both ATX-3 and CDC-48.1 mutants and, in addition, we identify a new protein interactor, UBXN-5, potentially an adaptor of the CDC-48-ATX-3 escort complex. CDC-48 binds to both ATX-3 and UBXN-5 in a non-competitive manner, suggesting the formation of a trimolecular complex. Both CDC-48 and ATX-3, but not UBXN-5, were able to bind K-48 polyubiquitin chains, the standard signal for proteasomal degradation. Additionally, we describe several common interactors of ATX-3 and UBXN-5, some of which can be in vivo targets of this complex.

• Authors: Ana-João Rodrigues, Andreia Neves-Carvalho, Anabela Ferro, Anne Rokka, Garry Corthals, Elsa Logarinho, Patrícia Maciel
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 386 Issue 4 Pg. 575-81 (Sep 04 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19545544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Caenorhabditis elegans Proteins
• Cell Cycle Proteins
• Multiprotein Complexes
• Nerve Tissue Proteins
• UBXN-5 protein, C elegans
• Ataxin-3
• atx-3 protein, C elegans
• Adenosine Triphosphatases
• Valosin Containing Protein

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Adenosine Triphosphatases (genetics, metabolism)
• Animals
• Ataxin-3
• Caenorhabditis elegans (genetics, metabolism)
• Caenorhabditis elegans Proteins (genetics, metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Multiprotein Complexes (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Protein Interaction Domains and Motifs (genetics)
• Protein Interaction Mapping
• Valosin Containing Protein