title: Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins.
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 AIPs 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, AIP4, 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.
authors.affiliation: Division of Neurobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Wood
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: R L
authors.initials: RL
authors.lastname: Margolis
authors.forename: V
authors.initials: V
authors.lastname: Colomer
authors.forename: K
authors.initials: K
authors.lastname: Duan
authors.forename: J
authors.initials: J
authors.lastname: Kushi
authors.forename: Z
authors.initials: Z
authors.lastname: Kaminsky
authors.forename: J J
authors.initials: JJ
authors.lastname: Kleiderlein
authors.forename: A H
authors.initials: AH
authors.lastname: Sharp
authors.forename: C A
authors.initials: CA
authors.lastname: Ross
mesh_terms: D000818:Animals; D000906:Antibodies; D001923:Brain Chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005333:Fetus / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D015003:Yeasts / Q000235:genetics
chemical_list: D000906:Antibodies; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C095278:atrophin-1