Post-translational modifications of the progesterone receptors.
Post-translational modifications of the progesterone receptors.
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DOI：
10.1016/j.jsbmb.2013.12.008
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发表时间：
2014-03
影响因子：
4.1
通讯作者：
Horwitz, Kathryn B.
中科院分区：
文献类型：
--
作者：
Abdel-Hafiz, Hany A.;Horwitz, Kathryn B.
关键词：
黄体酮在女性生殖组织的发育、分化和维持中起着关键作用，并具有多种非生殖神经功能。根据细胞和组织、激素环境、生长条件和发育阶段的不同，黄体酮既可以刺激细胞生长，也可以抑制细胞生长，同时促进分化。孕激素受体（PRs）属于类固醇激素受体超家族的配体依赖性转录因子。PR蛋白受到广泛的翻译后修饰，包括磷酸化、乙酰化、泛素化和sumo化。这些修饰之间的相互作用是复杂的，一个因素影响另一个因素对受体的影响。对这些修饰的控制是物种、组织和细胞特异性的。它们反过来调节多种功能，包括PR稳定性、亚细胞定位、蛋白-蛋白相互作用和转录活性。这些复杂性可能解释了组织和基因特异性调节差异是如何在同一生物体中由相同的受体蛋白和激素实现的。在这里，我们回顾了目前对PR翻译后修饰的了解，并讨论了这些修饰如何影响人类乳腺癌细胞的受体功能。还有很多东西需要学习。然而，我们对此的理解可能有助于确定以组织特异性，甚至基因特异性方式靶向PR活性的治疗药物。
Progesterone plays a key role in the development, differentiation and maintenance of female reproductive tissues and has multiple non-reproductive neural functions. Depending on the cell and tissue, the hormonal environment, growth conditions and the developmental stage, progesterone can either stimulate cell growth or inhibit it while promoting differentiation. Progesterone receptors (PRs) belong to the steroid hormone receptor superfamily of ligand-dependent transcription factors. PR proteins are subject to extensive post-translational modifications that include phosphorylation, acetylation, ubiquitination and SUMOylation. The interplay among these modifications is complex with alteration of the receptors by one factor influencing the impact of another. Control over these modifications is species-, tissue- and cell-specific. They in turn regulate multiple functions including PR stability, their subcellular localization, protein-protein interactions and transcriptional activity. These complexities may explain how tissue- and gene-specific differences in regulation are achieved in the same organism, by the same receptor protein and hormone. Here we review current knowledge of PR post-translational modifications and discuss how these may influence receptor function focusing on human breast cancer cells. There is much left to be learned. However, our understanding of this may help to identify therapeutic agents that target PR activity in tissue-specific, even gene-specific ways.
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影响因子：
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通讯作者：
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