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

Hitoshi Okazawa, 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

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)701-713
Number of pages13
Issue number5
StatePublished - May 30 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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