Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases

Adolfo Saiardi, Adam C. Resnick, Adele M. Snowman, Beverly Wendland, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

Abstract

Inositol pyrophosphates physiologically regulate vesicular endocytosis, ribosomal disposition, and directly phosphorylate proteins. Here we demonstrate roles in cell death and regulation of telomere length. Lethal actions of wortmannin and caffeine are selectively abolished in yeast mutants that cannot synthesize inositol pyrophosphates. Wortmannin and caffeine appear to act through the phosphoinositide 3-kinase-related protein kinases Tel1 and Mec1, known regulators of telomere length. Inositol pyrophosphates physiologically antagonize the actions of these kinases, which is demonstrated by the fact that yeast mutants with reduced or elevated levels of inositol pyrophosphates, respectively, display longer and shorter telomeres.

Original languageEnglish (US)
Pages (from-to)1911-1914
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number6
DOIs
StatePublished - Feb 8 2005

Keywords

  • Caffeine
  • Wortmannin
  • Yeast

ASJC Scopus subject areas

  • General

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