The BioGRID | PUBLICATION VIEW

	Neuron May (2002); 34(5):701-13
Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.
Okazawa H, Rich T, Chang A, Lin X, Waragai M, Kajikawa M, Enokido Y, Komuro A, Kato S, Shibata M, Hatanaka H, Mouradian MM, Sudol M, Kanazawa I
Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan. okazawa@tmin.ac.jp
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.
[PUBMED: 12062018]