Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death

Eiichiro Nagata, Hongbo R. Luo, Adolfo Saiardi, Byoung Il Bae, Norihiro Suzuki, Solomon H. Snyder

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Diphosphoinositol pentakisphosphate (InsP7) and bis-diphosphoinositol tetrakisphosphate contain pyrophosphate bonds. InsP7 is formed from inositol hexakisphosphate (InsP6) by a family of three inositol hexakisphosphate kinases (InsP6K). In this study we establish one of the InsP6Ks, InsP6K2, as a physiologic mediator of cell death. Overexpression of wild-type InsP6K2 augments the cytotosic actions of multiple cell stressors in diverse cell lines, whereas transfection with a dominant negative InsP6K2 decreases cell death. During cell death, InsP6 kinase activity is enhanced, and intracellular InsP7 level is augmented. Deletion of InsP6K2 but not the other forms of InsP6K diminishes cell death, suggesting that InsP6K2 is the major InsP6 kinase involved in cell death. Cytotoxicity is associated with a translocation of InsP6K2 from nuclei to mitochondria, whereas the intracellular localization of the other isoforms of the enzyme does not change. The present study provides compelling evidence that endogenous InsP6K2, by generating InsP7, provides physiologic regulation of the apoptotic process.

Original languageEnglish
Pages (from-to)1634-1640
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number2
DOIs
Publication statusPublished - 2005 Jan 14

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Nagata, E., Luo, H. R., Saiardi, A., Bae, B. I., Suzuki, N., & Snyder, S. H. (2005). Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. Journal of Biological Chemistry, 280(2), 1634-1640. https://doi.org/10.1074/jbc.M409416200