Formation of an IKKα-dependent transcription complex is required for estrogen receptor-mediated gene activation
Formation of an IKKα-dependent transcription complex is required for estrogen receptor-mediated gene activation
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DOI：
10.1016/j.molcel.2005.03.006
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发表时间：
2005-04-01
期刊：
影响因子：
16
通讯作者：
Gaynor, RB
中科院分区：
文献类型：
--
作者：
Park, KJ;Krishnan, V;Gaynor, RB
IKB激酶IKK α和IKK β调节不同的细胞质和细胞核事件，这些事件对于马槟榔碱介导的NF-B-K途径的活化至关重要。由于IKK先前已被证明与核激素受体辅激活因子AIB 1/SRC-3相关，因此解决了IKK α或IKK β是否参与增加细胞因子应答基因表达的问题。我们证明IKKa与ER α结合。和AIB 1/SRC-3，在激活雌激素应答基因（包括细胞周期蛋白D1和c-myc）的转录以导致乳腺癌细胞增殖增强中起重要作用。雌激素处理促进IKK α、ER α和AIB 1/SRC-3与雌激素应答启动子的结合，并增加ERet、AlB 1/ SRC-3和组蛋白H3的IKK α磷酸化。这些结果表明，IKK α通过其启动子缔合和转录复合物组分的修饰在调节雌激素的生物学效应中起主要作用。
The IKB kinases IKK alpha and IKK beta regulate distinct cytoplasmic and nuclear events that are critical for cytokine-mediated activation of the NF-B-K pathway. Because the IKKs have previously been demonstrated to associate with the nuclear hormone receptor coactivator AIB1/SRC-3, the question of whether either IKK alpha or IKK beta may be involved in increasing the expression of hormone-responsive genes was addressed. We demonstrated that IKKa, in conjunction with ER alpha. and AIB1/SRC-3, is important in activating the transcription of estrogen-responsive genes, including cyclin D1 and c-myc, to result in the enhanced proliferation of breast cancer cells. Estrogen treatment facilitated the association of IKK alpha, ER alpha and AIB1/SRC-3 to estrogen-responsive promoters and increased IKK alpha phosphorylation of ERet, AlB1/ SRC-3, and histone H3. These results suggest that IKK alpha plays a major role in regulating the biological effects of estrogen via its promoter association and modification of components of the transcription complex.