title: Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.
abstract: PQBP-1 was isolated on the basis of its interaction with polyglutamine tracts. In this study, using in vitro and in vivo assays, we show that the association between ataxin-1 and PQBP-1 is positively influenced by expanded polyglutamine sequences. In cell lines, interaction between the two molecules induces apoptotic cell death. As a possible mechanism underlying this phenomenon, we found that mutant ataxin-1 enhances binding of PQBP-1 to the C-terminal domain of RNA polymerase II large subunit (Pol II). This reduces the level of phosphorylated Pol II and transcription. Our results suggest the involvement of PQBP-1 in the pathology of spinocerebellar ataxia type 1 (SCA1) and support the idea that modified transcription underlies polyglutamine-mediated pathology.
authors.affiliation: Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan. okazawa@tmin.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazawa
authors.forename: Tina
authors.initials: T
authors.lastname: Rich
authors.forename: Alex
authors.initials: A
authors.lastname: Chang
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.forename: Masaaki
authors.initials: M
authors.lastname: Waragai
authors.forename: Masunori
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Enokido
authors.forename: Akihiko
authors.initials: A
authors.lastname: Komuro
authors.forename: Seishi
authors.initials: S
authors.lastname: Kato
authors.forename: Masao
authors.initials: M
authors.lastname: Shibata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatanaka
authors.forename: M Maral
authors.initials: MM
authors.lastname: Mouradian
authors.forename: Marius
authors.initials: M
authors.lastname: Sudol
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D000368:Aged; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005260:Female; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046911:Macromolecular Substances; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human; D010455:Peptides; C492272:Pqbp1 protein, mouse; C097188:polyglutamine; D012319:RNA Polymerase II