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

159 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)701-713
Number of pages13
JournalNeuron
Volume34
Issue number5
DOIs
StatePublished - May 30 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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