Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence
Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence
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DOI：
10.1006/excr.2001.5166
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发表时间：
2001-05-01
影响因子：
3.7
通讯作者：
Wright, EG
中科院分区：
文献类型：
--
作者：
Coates, PJ;Nenutil, R;Wright, EG
抑制蛋白（Prohibitin protein，BAP37）是一种具有多种功能的蛋白质，包括细胞周期调控、细胞凋亡、线粒体呼吸链酶组装和衰老等。我们表明哺乳动物的抑制蛋白存在于线粒体内膜中，并且总是相互结合，没有检测到游离蛋白。它们在发育期间和成年哺乳动物组织中共表达，并且表达水平指示在线粒体代谢中的作用，但与在细胞增殖或凋亡的调节中的作用不相容。蛋白质的高水平表达在原发性人类肿瘤中始终可见，而人类和鸡成纤维细胞的细胞衰老伴随着两种蛋白质的异质性降低。这两种蛋白质是由线粒体和核编码的线粒体蛋白质合成失衡引起的代谢应激诱导的，但对氧化应激、热休克或其他细胞应激没有反应。该基因启动子序列含有Myc癌蛋白的结合位点，Myc的过表达诱导了Escherubitins的表达。数据支持抑制素在调节线粒体呼吸活动和衰老中的保守作用。(C)北京：科学出版社.
The two prohibitin proteins, Phb1p and Phb2p(BAP37) hare been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging. (C) 2001 Academic Press.