期刊
ARCHIVES OF MEDICAL RESEARCH
卷 32, 期 6, 页码 576-586出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0188-4409(01)00338-1
关键词
cholesterol; mitochondria; steroidogenesis; steroidogenic acute regulatory protein; transcription
资金
- NICHD NIH HHS [HD06274] Funding Source: Medline
Steroidogenic acute regulatory (StAR) protein controls the rate-limiting step in steroidogenesis: the transport of cholesterol from the outer to the inner mitochondrial membrane. Early studies indicated that rate of transcription of the StAR gene is a primary determinant of steroidogenesis. The transcription factors that govern basal and cAMP-dependent StAR expression are reviewed, as are new findings regarding chromatin modifications associated with activation of the StAR promoter. Molecular genetic studies of congenital lipoid adrenal hyperplasia, a rare disease caused by mutations in the StAR gene, and structure-function studies defined two major domains within the StAR protein, the N-terminal mitochondrial targeting sequence and the C-terminal StAR-related lipid transfer (START) domain, which promotes the translocation of cholesterol between the two mitochondrial membranes. Several models of StAR's mechanism of action have been proposed based on a combination of structure/function studies or on the crystal structure of a related START domain. The models-intermembrane shuttle hypothesis, and cholesterol desorption hypothesis-are discussed with respect to the known biochemical and biophysical events associated with steroidogenesis and the structure of StAR. (C) 2001 IMSS. Published by Elsevier Science Inc.
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