Inositol hexakisphosphate kinases induce cell death in Huntington disease

Eiichiro Nagata, Adolfo Saiardi, Hideo Tsukamoto, Yoshinori Okada, Yoshiko Itoh, Tadayuki Satoh, Johbu Itoh, Russell L. Margolis, Shunya Takizawa, Akira Sawa, Shigeharu Takagi

Research output: Contribution to journalArticle

Abstract

Inositol pyrophosphate diphosphoinositol pentakisphosphate is ubiquitously present in mammalian cells and contains highly energetic pyrophosphate bonds. We have previously reported that inositol hexakisphosphate kinase type 2 (InsP 6K2), which converts inositol hexakisphosphate to inositol pyrophosphate diphosphoinositol pentakisphosphate, mediates apoptotic cell death via its translocation from the nucleus to the cytoplasm. Here, we report that InsP 6K2 is localized mainly in the cytoplasm of lymphoblast cells from patients with Huntington disease (HD), whereas this enzyme is localized in the nucleus in control lymphoblast cells. The large number of autophagosomes detected in HD lymphoblast cells is consistent with the down-regulation of Akt in response to InsP 6K2 activation. Consistent with these observations, the overexpression of InsP 6Ks leads to the depletion of Akt phosphorylation and the induction of cell death. These results suggest that InsP 6K2 activation is associated with the pathogenesis of HD.

Original languageEnglish (US)
Pages (from-to)26680-26686
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number30
DOIs
StatePublished - Jul 29 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Nagata, E., Saiardi, A., Tsukamoto, H., Okada, Y., Itoh, Y., Satoh, T., Itoh, J., Margolis, R. L., Takizawa, S., Sawa, A., & Takagi, S. (2011). Inositol hexakisphosphate kinases induce cell death in Huntington disease. Journal of Biological Chemistry, 286(30), 26680-26686. https://doi.org/10.1074/jbc.M111.220749