Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 111, Issue 5, Pages 1367-1374Publisher
WILEY
DOI: 10.1002/jcb.22865
Keywords
PROHIBITIN; CHOLESTEROL; CELL CYCLE; PROSTATE CANCER
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Funding
- NIH [R01 CA101046]
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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.
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