Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes
Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes
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DOI：
10.1073/pnas.95.6.2920
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发表时间：
1998-03-17
影响因子：
11.1
通讯作者：
Rose, DW
中科院分区：
文献类型：
--
作者：
Lavinsky, RM;Jepsen, K;Rose, DW
几条证据表明，核受体辅阻遏物（N-CoR）复合物对视黄酸受体的转录激活施加配体依赖性，并介导雌激素受体拮抗剂（如他莫昔芬）的抑制作用，抑制组成性N末端、Creb结合蛋白/辅激活物复合物依赖性激活结构域，调节特异性受体与N-CoR或SMRT辅阻遏物复合物之间的功能性相互作用，通过不同的信号转导途径，N-CoR水平的降低与人乳腺癌小鼠模型系统中他莫昔芬耐药性的获得相关。我们的数据表明，N-CoR-和SMRT-含有复合物作为限速组件的行动，具体的核受体，他们的行动是由多个信号转导途径调节。
Several lines of evidence indicate that the nuclear receptor corepressor (N-CoR) complex imposes ligand dependence on transcriptional activation by the retinoic acid receptor and mediates the inhibitory effects of estrogen receptor antagonists, such as tamoxifen, suppressing a constitutive N-terminal, Creb-binding protein/coactivator complex-dependent activation domain, Functional interactions between specific receptors and N-CoR or SMRT corepressor complexes are regulated, positively or negatively, by diverse signal transduction pathways, Decreased levels of N-CoR correlate with the acquisition of tamoxifen resistance in a mouse model system for human breast cancer. Our data suggest that N-CoR- and SMRT-containing complexes act as rate-limiting components in the actions of specific nuclear receptors, and that their actions are regulated by multiple signal transduction pathways.