Interplay between two hormone-independent activation domains in the androgen receptor
Interplay between two hormone-independent activation domains in the androgen receptor
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DOI：
10.1158/0008-5472.can-05-2389
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发表时间：
2006-01-01
期刊：
影响因子：
11.2
通讯作者：
Claessens, F
中科院分区：
文献类型：
--
作者：
Callewaert, L;Van Tilborgh, N;Claessens, F
雄激素受体（AR）在前列腺癌的发展及其治疗中起着关键作用，即使是对于前列腺癌难治性状态。在这里，我们报告说，早期描述的赖氨酸到精氨酸突变的位置179 AR导致更有效的AR。我们表明，两个激活域（Tau-1和Tau-5）是必要的，充分的AR的活性和AR-NTD的内在活性。围绕Lys（179）的两个α-螺旋定义了Tau-1的核心，它可以作为独立于p160共激活因子的自主激活功能。此外，我们表明，虽然招聘的p160辅激活因子介导的Tau-5，这一事件是衰减的核心Tau-1。这种对Tau-1和Tau-5作用机制的更好定义有助于设计针对前列腺癌的替代治疗策略。
The androgen receptor (AR) plays a key role in prostate cancer development, as well as its treatments, even for the hormone-refractory state. Here, we report that an earlier described lysine-to-arginine mutation at position 179 in AR leads to a more potent AR. We show that two activation domains (Tau-1 and Tau-5) are necessary and sufficient for the full activity of AR and the intrinsic activity of the AR-NTD. Two alpha-helices surrounding the Lys(179) define the core of Tau-1, which can act as an autonomous activation function, independent of p160 coactivators. Furthermore, we show that although the recruitment of p160 coactivators is mediated through Tau-5, this event is attenuated by core Tau-1. This better definition of the mechanisms of action of both Tau-1 and Tau-5 is instrumental for the design of alternative therapeutic strategies against prostate cancer.