Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor

Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor
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DOI:
10.1016/j.bbrc.2005.12.167
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发表时间:
2006-03-03
影响因子:
3.1
通讯作者:
Yanase, T
Yanase, T
中科院分区:
生物学4区
文献类型:
--
作者:
Fan, SL;Goto, K;Yanase, T

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此前,我们发现了人雄激素受体(AR)激活功能-1(AF-1)结构域的转录共激活因子,并将其命名为雄激素受体N末端结构域反式激活蛋白-1(ANT-1)。这种共激活子包含来自氨基酸(AA)294的多个四肽重复(TPR)基序,与U5小核核糖核蛋白颗粒的一个成分相同,并与AR或糖皮质激素受体特异性结合。在这里,我们确定了四个不同的功能域。AR-AF-1结合结构域与AR-AF-1中的AA180-360或360-532结合,与TAU-1和TAU-5明显重叠。ANT-1的这个结构域和亚核斑点形成结构域被指定在TPR基序中,而反式激活和核定位信号域则位于N-末端序列中。这些功能结构域的存在可能进一步支持这样的观点,即ANT-1在介导转录-剪接耦合的同时可以作为AR-AF-1特异性的共激活因子发挥作用。(C)2005 Elsevier Inc.保留所有权利。
Previously, we identified a transcriptional coactivator for the activation function-1 (AF-1) domain of the human androgen receptor (AR) and designated it androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from amino acid (aa) 294, is identical to a component of U5 small nuclear ribonucleoprotein particles and binds specifically to the AR or glucocorticoid receptor. Here, we identified four distinct functional domains. The AR-AF-1-binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation domain in ANT-1 were assigned within the TPR motifs, while the transactivating and nuclear localization signal domains resided within the N-terminal sequence. The existence of these functional domains may further support the idea that ANT-1 can function as an AR-AF-1-specific coactivator while mediating a transcription-splicing coupling. (c) 2005 Elsevier Inc. All rights reserved.