Guo Ing-Cherng, Shih Meng-Chun, Lan Hsin-Chieh, Hsu Nai-Chi, Hu Meng-Chun, Chung Bon-Chu
Department of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
J Biomed Sci. 2007 Jul;14(4):509-15. doi: 10.1007/s11373-007-9177-z. Epub 2007 Jun 27.
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.
CYP11A1基因编码胆固醇侧链裂解酶，也称为细胞色素P450scc，它在线粒体类固醇生物合成的第一步中催化胆固醇转化为孕烯醇酮。CYP11A1在肾上腺和性腺中的选择性表达，受激素和发育调控，主要由其2.3 kb的启动子驱动。多种反式作用因子，如SF-1、Sp1、AP-2、TReP-132、LBP-1b、LBP-9、AP-1、NF-1和Ets，通过与它们特定的顺式作用元件进行DNA-蛋白质相互作用，或通过彼此之间的蛋白质-蛋白质相互作用来控制CYP11A1的转录，其中SF-1在肾上腺和睾丸中起核心作用。除了与其近端和上游基序结合外，SF-1还与TFIIB、CBP/p300、TReP-132和c-Jun/AP-1进行物理相互作用，以特异性传递cAMP的调节信号。其他因子，如Sp1家族成员、AP-2和LBP-1b/LBP-9，可能是在CYP11A1转录中起作用的其他因子，特别是在胎盘细胞中。TATA序列也可能有助于CYP11A1转录的组织特异性和激素调节。本文综述了近期针对肾上腺和性腺的研究。
