title: Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases.
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.
authors.affiliation: Department of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Saiardi
authors.forename: Adam C
authors.initials: AC
authors.lastname: Resnick
authors.forename: Adele M
authors.initials: AM
authors.lastname: Snowman
authors.forename: Beverly
authors.initials: B
authors.lastname: Wendland
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000730:Androstadienes / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002110:Caffeine; D005656:Fungal Proteins; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D000077191:Wortmannin; C088937:MEC1 protein, S cerevisiae; C513623:TEL1 protein, S cerevisiae