A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors
A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors
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DOI：
10.1016/s0092-8674(00)81118-6
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发表时间：
1996-05-03
期刊：
影响因子：
64.5
通讯作者：
Rosenfeld, MG
中科院分区：
文献类型：
--
作者：
Kamei, Y;Xu, L;Rosenfeld, MG
核受体通过直接激活靶基因和抑制AP-1来调节基因表达。在这里，我们报告说，出乎意料的是，激活核受体需要CREB结合蛋白（CBP）的行动和AP-1活性的抑制是竞争的CBP/p300在细胞中的数量有限的明显结果。利用不同的结构域，CBP直接与多个核受体的配体结合结构域和p160核受体辅激活因子相互作用，克隆后已被证明是SRC-1蛋白的变体。由于CBP代表了一个共同的因素，除了核受体，CREB和AP-1的功能不同的共激活剂，我们建议CBP/p300作为一个集成器的多个信号转导通路的细胞核内。
Nuclear receptors regulate gene expression by direct activation of target genes and inhibition of AP-1. Here we report that, unexpectedly, activation by nuclear receptors requires the actions of CREB-binding protein (CBP) and that inhibition of AP-1 activity is the apparent result of competition for limiting amounts of CBP/p300 in cells. Utilizing distinct domains, CBP directly interacts with the ligand-binding domain of multiple nuclear receptors and with the p160 nuclear receptor coactivators, which upon cloning have proven to be variants of the SRC-1 protein. Because CBP represents a common factor, required in addition to distinct coactivators for function of nuclear receptors, CREB, and AP-1, we suggest that CBP/p300 serves as an integrator of multiple signal transduction pathways within the nucleus.