Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin S C, Heyman R A, Rose D W, Glass C K, Rosenfeld M G
Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, 92093-0648, USA.
Cell. 1996 May 3;85(3):403-14. doi: 10.1016/s0092-8674(00)81118-6.
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.
核受体通过直接激活靶基因和抑制AP-1来调节基因表达。在此我们报告，出乎意料的是，核受体的激活需要CREB结合蛋白（CBP）的作用，并且对AP-1活性的抑制显然是细胞中有限量的CBP/p300竞争的结果。利用不同的结构域，CBP直接与多种核受体的配体结合结构域以及p160核受体共激活因子相互作用，克隆后发现这些共激活因子是SRC-1蛋白的变体。由于CBP是核受体、CREB和AP-1功能所需的除不同共激活因子之外的一个共同因子，我们认为CBP/p300作为细胞核内多种信号转导途径的整合者。
