Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation
Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation
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DOI：
10.1074/jbc.m312563200
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发表时间：
2004-02-20
影响因子：
4.8
通讯作者：
Lee, JW
中科院分区：
文献类型：
--
作者：
Goo, YH;Na, SY;Lee, JW
活化信号共整合子-2（ASC-2）是核受体和许多其他转录因子的癌症扩增转录共活化子，先前已显示含有两个LXXLL基序，每个基序与一组不同的核受体相互作用。在这项工作中，我们发现ASC-2有一个间接的，单独的雄激素受体（AR）的结合位点。有趣的是，该区域与肿瘤抑制因子视网膜母细胞瘤（Rb）的直接相互作用界面重叠。虽然ASC-2单独刺激AR反式激活共转染的HeLa细胞，Rb异位表达的影响ASC-2作为一个转录共激活剂的AR在Rb无效Saos 2细胞。这些结果，沿着先前的报道，其中AR显示与Rb直接相互作用（Yeh，S.，Miyamoto，H.，Nishimura，K.，康，H.，卢德洛，J.，Hsiao，P.，Wang，C.，苏，C.，和Chang C.等人（1998）Biochem. Biophys.通信资源248，361-367），表明体内AR-ASC-2相互作用可能涉及Rb。因此，ASC-2似乎含有至少三个不同的核受体相互作用结构域。
Activating signal cointegrator-2 (ASC-2), a cancer-amplified transcription coactivator of nuclear receptors and numerous other transcription factors, was previously shown to contain two LXXLL motifs, each of which interacts with a distinct set of nuclear receptors. In this work, we showed that ASC-2 has an indirect, separate binding site for androgen receptor (AR). Interestingly, this region overlapped with the direct interaction interfaces with the tumor suppressor retinoblastoma (Rb). Although ASC-2 alone stimulated AR transactivation in cotransfections of HeLa cells, ectopic expression of Rb effected ASC-2 to act as a transcription coactivator of AR in Rb-null Saos2 cells. These results, along with the previous report in which AR was shown to directly interact with Rb (Yeh, S., Miyamoto, H., Nishimura, K., Kang, H., Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang C. (1998) Biochem. Biophys. Res. Commun. 248, 361-367), suggest that the AR-ASC-2 interactions in vivo may involve Rb. Thus, ASC-2 appears to contain at least three distinct nuclear receptor interaction domains.