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

90 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

Fingerprint

Cell death
Cell Death
Phosphotransferases
Phytic Acid
Mitochondria
Cytotoxicity
Transfection
Protein Isoforms
Cells
inositol hexakisphosphate kinase
Cell Line
inositol heptakisphosphate
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. / Nagata, Eiichiro; Luo, Hongbo R.; Saiardi, Adolfo; Bae, Byoung Il; Suzuki, Norihiro; Snyder, Solomon H.

In: Journal of Biological Chemistry, Vol. 280, No. 2, 14.01.2005, p. 1634-1640.

Research output: Contribution to journalArticle

Nagata, E, Luo, HR, Saiardi, A, Bae, BI, Suzuki, N & Snyder, SH 2005, 'Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death', Journal of Biological Chemistry, vol. 280, no. 2, pp. 1634-1640. https://doi.org/10.1074/jbc.M409416200
Nagata, Eiichiro ; Luo, Hongbo R. ; Saiardi, Adolfo ; Bae, Byoung Il ; Suzuki, Norihiro ; Snyder, Solomon H. / Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 2. pp. 1634-1640.
@article{fdf0bbfcfa3447c0aa01d872cfb88a9a,
title = "Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death",
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.",
author = "Eiichiro Nagata and Luo, {Hongbo R.} and Adolfo Saiardi and Bae, {Byoung Il} and Norihiro Suzuki and Snyder, {Solomon H.}",
year = "2005",
month = "1",
day = "14",
doi = "10.1074/jbc.M409416200",
language = "English",
volume = "280",
pages = "1634--1640",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "2",

}

TY - JOUR

T1 - Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death

AU - Nagata, Eiichiro

AU - Luo, Hongbo R.

AU - Saiardi, Adolfo

AU - Bae, Byoung Il

AU - Suzuki, Norihiro

AU - Snyder, Solomon H.

PY - 2005/1/14

Y1 - 2005/1/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=12544255427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12544255427&partnerID=8YFLogxK

U2 - 10.1074/jbc.M409416200

DO - 10.1074/jbc.M409416200

M3 - Article

C2 - 15533939

AN - SCOPUS:12544255427

VL - 280

SP - 1634

EP - 1640

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 2

ER -