Physiological and pathological functions of PQBP-1

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12670596
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: OKAZAWA Hitoshi Univ. Tokyo, Dept. Neurology, Res. Associate, 医学部・附属病院, 助手 (50261996)
• Project Period (FY): 2000 – 2001
• Keywords: PQBP-1 / polyglutamine / transcription / cell death / neuron / spinocerebellar degeneration

Research Abstract

In this project, we have analyzed physiological and pathological functions of PQBP-1, which we found as a novel binding protein to the polyglutamine sequences. First, we found that PQBP-1 also interacts with ataxin-1, a causative gene product of SCA1, and induces transcriptional repression cooperatively. The interaction between PQBP-1 and ataxin-1 inhibits transcription not in the inclusion body but in the nuclear matrix, suggesting a new cascade of pathogenesis. Furthermore, our study showed that the interaction leads to reduction of phosphorylated form (=active form) of RNA polymerase II. These results, together with transgenic mouse of PQBP-1, will contribute for understanding this type of neurodegenerative diseases.

Research Products

• [Publications] Shoji, M. et al.: "JNK activation is associated with intracellular β-amyloid accumulation"Molecular Brain Research. 85. 221-233 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Okazawa, H. et al.: "PQBP-1 (Np/PQ) : A polyglutamine tract binding and nuclear inclusion-formin protein"Brain Research Bulletin. 56. 273-280 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ueda H, Goto J, Hashida H, Lin X, Oyanagi K, kawano H, et al.: "Enhanced SUMOylation in polyglutamine diseases"Biochem. Biophys. Res. Commun.. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Okazawa H, Rich T, Chang A, Lin X, Waragai M, et al.: "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death"Neuron. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shoji M., Iwakami N., Takeuchi S., Waragai M., Suzuki M., Kanazawa M., Lippa C.F., Ono S. and Okazawa H.: "JNK activation is associated with intracellular beta-amyloid accumulation."Molecular Brain Research. 85. 221-233 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Okazawa H., Sudol, M. and Rich, T.: "PQBP-1 (Np/PQ): a polyglutamine tract-binding and nuclear inclusion-forming protein."Brain Res Bull.. 56. 273-280 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ueda H., Goto J., Hashida H., Lin X., Oyanagi K., Kawano H., Zoghbi H.Y., Kanazawa I., and Okazawa H.: "Enhanced SUMOylation in polyglutamine diseases."Biochem. Biophys. Res. Commun.. (in press). (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Okazawa H.. Rich T., Chang A., Lin X., Waragai M., Kajikawa M., Enokido Y., Komuo A., Kato S., Shibata M., Hatanaka H., Mouradian M.M., Sudol M., Kanazawa I.: "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death."Neuron. (in press). (2002)
  • Description: 「研究成果報告書概要(欧文)」より