The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR).

The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR).
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DOI:
10.1016/s0021-9258(18)46930-x
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发表时间:
1994-11
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
B. Clark;J. Wells;S. King;D. Stocco
B. Clark;J. Wells;S. King;D. Stocco
中科院分区:
其他
文献类型:
--
作者:
B. Clark;J. Wells;S. King;D. Stocco

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类固醇生成细胞对营养激素刺激的急性反应是将胆固醇从细胞储存库动员到线粒体外膜,并将该胆固醇转移到线粒体内膜,在线粒体内膜中发生类固醇生成的第一个酶促步骤。胆固醇跨线粒体膜的转移依赖于蛋白质的从头合成,这是该过程中的调节步骤。虽然新合成的调节蛋白尚未被鉴定,但我们先前已经提出了一种候选蛋白,我们在MA-10细胞中鉴定了该候选蛋白,其响应于促黄体激素刺激而合成,并且定位于线粒体。在本研究中,我们报告分离的cDNA编码这种促黄体生成激素诱导的蛋白质。cDNA和蛋白质序列分析表明这是一种新的蛋白质。重要的是,我们第一次证明了在没有激素刺激的情况下,MA-10细胞中蛋白质的表达足以诱导类固醇产生。我们的结论是,这种蛋白质是必需的类固醇生成的急性调节,并建议将这种蛋白质的类固醇生成急性调节蛋白(星星)。
The acute response of steroidogenic cells to trophic hormone stimulation is the mobilization of cholesterol from cellular stores to the mitochondrial outer membrane and the transfer of this cholesterol to the mitochondrial inner membrane where the first enzymatic step in steroidogenesis occurs. The transfer of cholesterol across the mitochondrial membranes is dependent upon de novo protein synthesis, and this is the regulated step in the process. Although the newly synthesized regulatory protein(s) have yet to be identified, we previously have proposed a candidate protein which we identified in MA-10 cells that is synthesized in response to luteinizing hormone stimulation and that is localized to the mitochondria. In the present study, we report the isolation of a cDNA that encodes this luteinizing hormone-induced protein. Analysis of the cDNA and protein sequences reveals this is a novel protein. Importantly, we demonstrate for the first time that expression of the protein in MA-10 cells in the absence of hormone stimulation is sufficient to induce steroid production. We conclude that this protein is required in the acute regulation of steroidogenesis and propose to call this protein the Steroidogenic Acute Regulatory protein (StAR).