Inositol Pyrophosphates Regulate Cell Death and Telomere Length Through Phosphoinositide 3-kinase-related Protein Kinases

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Jan 25

PMID 15665079

Citations 87

Authors

Adolfo Saiardi

Adam C Resnick

Adele M Snowman

Beverly Wendland

Solomon H Snyder

Affiliations

Soon will be listed here.

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.

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