Prohibitin Is a Cholesterol-Sensitive Regulator of Cell Cycle Transit
Prohibitin Is a Cholesterol-Sensitive Regulator of Cell Cycle Transit
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DOI：
10.1002/jcb.22865
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Solomon, Keith R.
中科院分区：
文献类型：
--
作者：
Dong, Pei;Flores, Jessica;Solomon, Keith R.
胆固醇在建立大多数功能性动物细胞膜中是必不可少的;在没有足够胆固醇的情况下，细胞不能生长或增殖。因此，几乎每个细胞，组织和动物都严格调节胆固醇稳态，包括胆固醇分子合成，运输，摄取和处置的复杂机制。我们假设细胞识别胆固醇不足导致细胞周期停滞，以避免膜合成的灾难性失败。在这里，我们证明了使用无偏见的蛋白质组学和标准的生物化学，胆固醇不足导致的抑制剂，细胞周期进程的抑制剂，通过激活胆固醇响应启动子元件的上调。我们还证明了抑制素保护细胞免于胆固醇不足引起的细胞凋亡。这是第一个将胆固醇稳态与抑制细胞凋亡的特定细胞周期调节剂联系起来的研究。J.细胞。111：1367-1374，2010. (C)2010 Wiley-Liss，Inc.
Cholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol-responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367-1374, 2010. (C) 2010 Wiley-Liss, Inc.