Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins

Jonathan D. Wood, Joseph Yuan, Russell L. Margolis, Veronica Colomer, Kui Duan, Jonathan Kushi, Zachary Kaminsky, John J. Kleiderlein, Alan H. Sharp, Christopher A. Ross

Research output: Contribution to journalArticlepeer-review

Abstract

Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy (DRPLA). The normal function of atrophin-1 is unknown. We have identified five atrophin-1 interacting proteins (AIPs) which bind to atrophin-1 in the vicinity of the polyglutamine tract using the yeast two-hybrid system. Four of the interactions were confirmed using in vitro binding assays. All five interactors contained multiple WW domains. Two are novel. The AlPs can be divided into two distinct classes. AIP1 and AIP3/WWP3 are MAGUK-like multidomain proteins containing a number of protein-protein interaction modules, namely a guanylate kinase-like region, two WW domains, and multiple PDZ domains. AIP2/WWP2, ALP4, and AIP5/WWP1 are highly homologous, each having four WW domains and a HECT domain characteristic of ubiquitin ligases. These interactors are similar to recently isolated huntingtin-interacting proteins, suggesting possible commonality of function between two proteins responsible for very similar diseases.

Original languageEnglish (US)
Pages (from-to)149-160
Number of pages12
JournalMolecular and Cellular Neurosciences
Volume11
Issue number3
DOIs
StatePublished - Jun 1998

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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