Transcriptional regulation of human CYP11A1 in gonads and adrenals
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- 作者：Ing-Cherng Guo ; Meng-Chun Shih ; Hsin-Chieh Lan ; Nai-Chi Hsu ; Meng-Chun Hu and Bon-chu Chung
- 关键词：CYP11A1 ; P450scc ; cholesterol side ; chain cleavage enzyme ; SF ; 1 ; adrenal ; steroidogenesis ; steroid ; gonad ; transcription
- 刊名：Journal of Biomedical Science
- 出版时间：July, 2007
- 出版年：2007
- 期刊代码：123_1021-7770
- 类别：bio
- 卷：14
- 期：4
- 页码：509-515
- 数据来源：sp
摘要
The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme, also termed cytochrome P450scc, which catalyzes the conversion of cholesterol to pregnenolone in the first step of steroid biosynthesis in mitochondria. The adrenal- and gonad-selective, hormonally and developmentally regulated expression of CYP11A1 is principally driven by its 2.3 kb promoter. Multiple trans-acting factors like SF-1, Sp1, AP-2, TReP-132, LBP-1b, LBP-9, AP-1, NF-1, and Ets control CYP11A1 transcription either through DNA-protein interaction with their specific cis-acting elements or through protein-protein interaction between each other, wherein SF-1 plays a central role in adrenals and testes. In addition to binding with its proximal and upstream motifs, SF-1 also physically interacts with TFIIB, CBP/p300, TReP-132, and c-Jun/AP-1 to specifically transmit the regulatory signals of cAMP. Other factors like Sp1 family members, AP-2, and LBP-1b/LBP-9 may be other factors that play a role in CYP11A1 transcription, particularly in placental cells. The TATA sequence could also contribute to tissue-specificity and hormonal regulation of CYP11A1 transcription. This article reviews recent studies focusing on adrenals and gonads.