肌醇焦磷酸通过磷脂酰肌醇3激酶相关蛋白激酶调节细胞死亡和端粒长度。
Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases.
作者信息
Saiardi Adolfo, Resnick Adam C, Snowman Adele M, Wendland Beverly, Snyder Solomon H
机构信息
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.
出版信息
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1911-4. doi: 10.1073/pnas.0409322102. Epub 2005 Jan 21.
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.
摘要
肌醇焦磷酸在生理上调节囊泡内吞作用、核糖体分布，并直接使蛋白质磷酸化。在此我们证明了其在细胞死亡和端粒长度调节中的作用。渥曼青霉素和咖啡因的致死作用在无法合成肌醇焦磷酸的酵母突变体中被选择性消除。渥曼青霉素和咖啡因似乎通过磷脂酰肌醇3激酶相关蛋白激酶Tel1和Mec1发挥作用，这两种激酶是已知的端粒长度调节因子。肌醇焦磷酸在生理上拮抗这些激酶的作用，这一事实表明，分别具有降低或升高水平肌醇焦磷酸的酵母突变体，其端粒显示出更长和更短的长度。
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