Physical and functional interactions between Daxx and TSG101.
Physical and functional interactions between Daxx and TSG101.
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DOI：
10.1016/j.bbrc.2004.02.126
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发表时间：
2004-04
影响因子：
3.1
通讯作者：
R. Muromoto;K. Sugiyama;Tetsuya Yamamoto;K. Oritani;Kazuya Shimoda;T. Matsuda
中科院分区：
文献类型：
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作者：
R. Muromoto;K. Sugiyama;Tetsuya Yamamoto;K. Oritani;Kazuya Shimoda;T. Matsuda
已报道Daxx介导细胞质中的Fas/JNK依赖性信号。然而，一些证据表明Daxx主要位于细胞核中，并作为转录调节因子发挥作用。最近，我们通过酵母双杂交筛选确定了DMAP 1（一种与TSG 101相互作用的蛋白质）作为Daxx结合伴侣。TSG 101已被证明是核激素受体的转录共阻遏物。在这里，我们研究了TSG 101是否也直接与Daxx相互作用。使用共表达的标记蛋白证实了Daxx和TSG 101的缔合。还绘制了两种蛋白质中的相互作用区域，并检查了相互作用的细胞定位。TSG 101通过其卷曲螺旋结构域与Daxx形成复合物并共定位于细胞核中。此外，TSG 101增强了Daxx介导的糖皮质激素受体转录活性抑制。这些结果提供了Daxx和TSG 101之间的新的分子相互作用，这在细胞核中建立了有效的抑制性转录复合物。
Daxx has been reported to mediate the Fas/JNK-dependent signals in the cytoplasm. However, several evidences have suggested that Daxx is located mainly in the nucleus and functions as a transcriptional regulator. Recently, we identified DMAP1, a TSG101-interacting protein as a Daxx binding partner by yeast two-hybrid screening. TSG101 has been shown to act as transcriptional co-repressor of nuclear hormone receptors. Here we examined whether TSG101also interacts with Daxx directly. The association of Daxx and TSG101 was confirmed using co-expressed tagged proteins. The interaction regions in both proteins were also mapped, and the cellular localization of the interaction was examined. TSG101 formed a complex with Daxx through its coiled-coil domain and co-localized in the nucleus. Furthermore, TSG101 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. These results provide the novel molecular interactions between Daxx and TSG101, which establish an efficient repressive transcription complex in the nucleus.