Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1
Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1
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DOI：
10.4049/jimmunol.172.5.2985
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Matsuda, T
中科院分区：
文献类型：
--
作者：
Muromoto, R;Sugiyama, K;Matsuda, T
Daxx已被证明在I型IFN-α介导的B细胞发育和凋亡抑制中起重要作用。最近，我们证明Tyk 2直接参与IFN信号传导以诱导和易位Daxx，这可能导致B淋巴细胞祖细胞的生长停滞和/或凋亡。为了阐明Daxx如何调节B细胞发育，我们通过酵母双杂交筛选来检查Daxx相互作用的伴侣。DNA甲基转移酶I（DNMT 1）相关蛋白（DMAP 1）被鉴定并证明与Daxx相互作用。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。Daxx和DMAP 1与DNMT 1形成复合物并共定位于细胞核中。DMAP 1增强了Daxx介导的糖皮质激素受体转录活性抑制。此外，Daxx在体内保护DMAP 1的蛋白质降解。这些结果提供了Daxx和DNMT 1之间的新的分子联系，其在细胞核中建立了抑制性转录复合物。
Daxx has been shown to play an essential role in type I IFN-alphabeta-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify how Daxx regulates B cell development, we examined Daxx interacting partners by yeast two-hybrid screening. DNA methyltransferase I (DNMT1)-associated protein (DMAP1) was identified and demonstrated to interact with Daxx. The interaction regions in both proteins were mapped, and the cellular localization of the interaction was examined. Both Daxx and DMAP1 formed a complex with DNMT1 and colocalized in the nucleus. DMAP1 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. Furthermore, Daxx protected protein degradation of DMAP1 in vivo. These results provide the novel molecular link between Daxx and DNMT1, which establishes a repressive transcription complex in the nucleus.