Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death

Neuron. 2002 May 30;34(5):701-13. doi: 10.1016/s0896-6273(02)00697-9.

Hitoshi Okazawa ¹, Tina Rich, Alex Chang, Xi Lin, Masaaki Waragai, Masunori Kajikawa, Yasushi Enokido, Akihiko Komuro, Seishi Kato, Masao Shibata, Hiroshi Hatanaka, M Maral Mouradian, Marius Sudol, Ichiro Kanazawa

Affiliations

Affiliation

1 Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan. okazawa@tmin.ac.jp

PMID: 12062018 DOI: 10.1016/s0896-6273(02)00697-9

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.

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