Molecular cell biology of androgen receptor signalling
Molecular cell biology of androgen receptor signalling
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DOI：
10.1016/j.biocel.2009.11.013
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发表时间：
2010-06-01
影响因子：
4
通讯作者：
Gobe, Glenda C.
中科院分区：
文献类型：
--
作者：
Bennett, Nigel C.;Gardiner, Robert A.;Gobe, Glenda C.
雄激素受体（AR）的经典作用是通过AR核转位调节基因转录过程。应答元件结合和转录因子AR的募集或与转录因子AR的串扰也利用信号转导的非经典、非基因组机制。这些机制先于基因转录或蛋白质合成，并涉及类固醇诱导的细胞质或细胞膜结合调节蛋白的调节。尽管进行了数十年的研究，AR在细胞和组织的基因调节中的作用仍然只是部分表征的AR在身体的性器官依赖性组织中发挥其大部分作用，但该受体也在许多以前认为不是雄激素敏感的组织中表达。因此，很可能存在AR的复杂的、更过度的作用。每个AR结构域通过细胞和组织发育和维持所必需的多种相互作用伴侣分子来协调多种个体和重要的作用。可表现出包括雄激素不敏感综合征和前列腺癌在内的多种临床表现。在恶性前列腺癌的情况下，治疗通常围绕设计用于干扰AR作用和雄激素信号传导轴的雄激素剥夺疗法，用于前列腺癌的雄激素疗法经常失败，突出了增加对AR功能的研究的真实的需要。(C)2009爱思唯尔有限公司版权所有
The classical action of androgen receptor (AR) is to regulate gene transcriptional processes via AR nuclear translocation. response element binding and recruitment of, or crosstalk with, transcription factors AR also utilises non-classical, non-genomic mechanisms of signal transduction These precede gene transcription or protein synthesis, and involve steroid-Induced modulation of cytoplasmic or cell membrane-bound regulatory proteins Despite many decades of investigation, the role of AR in gene regulation of cells and tissues remains only partially characterised AR exerts most of its effects in sex hormone-dependent tissues of the body, but the receptor is also expressed in many tissues not previously thought to be androgen sensitive. Thus it is likely that a complex, more over-arching, role for AR exists Each AR domain co-ordinates a multitude of individual and vital roles via a diverse array of interacting partner molecules that are necessary for cellular and tissue development and maintenance Aberrant AR activity, promoted by mutations or binding partner misregulation, can present as many clinical manifestations including androgen insensitivity syndrome and prostate cancer In the case of malignant prostate cancer, treatment generally revolves around androgen deprivation therapies designed to interfere with AR action and the androgen signalling axis Androgen therapies for prostate cancer often fail, highlighting a real need for increased research Into AR function. (C) 2009 Elsevier Ltd All rights reserved