Li Xiaolin, Kimbrel Erin A, Kenan Daniel J, McDonnell Donald P
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Mol Endocrinol. 2002 Jul;16(7):1482-91. doi: 10.1210/mend.16.7.0860.
The unliganded thyroid hormone receptor beta (TRbeta) represses the basal transcriptional activity of target genes, in part through interactions with the nuclear receptor corepressor (N-CoR). In this study we have identified a rather unexpected interaction between N-CoR and the nuclear receptor coactivator ACTR. We have demonstrated in vitro and in intact cells that N-CoR directly associates with ACTR and that the interaction surfaces on N-CoR and ACTR are distinct from those required for TR binding. The significance of this finding was demonstrated by showing that N-CoR facilitates an interaction between unliganded-TRbeta and ACTR. One possible consequence of the formation of the trimeric complex of N-CoR/ACTR/unliganded-TR is that N-CoR may raise the local concentration of ACTR at target gene promoters. In support of this hypothesis it was demonstrated that the presence of N-CoR can enhance TRbeta-mediated transcriptional activation. It is proposed, therefore, that TRbeta- mediated activation and repression are integrally linked in a manner that is not predicted by the current models of nuclear receptor action.
未结合配体的甲状腺激素受体β（TRβ）可抑制靶基因的基础转录活性，部分是通过与核受体共抑制因子（N-CoR）相互作用实现的。在本研究中，我们发现了N-CoR与核受体共激活因子ACTR之间一种相当意外的相互作用。我们已在体外和完整细胞中证明，N-CoR直接与ACTR缔合，且N-CoR和ACTR上的相互作用表面与TR结合所需的表面不同。通过表明N-CoR促进未结合配体的TRβ与ACTR之间的相互作用，证明了这一发现的重要性。N-CoR/ACTR/未结合配体的TR三聚体复合物形成的一个可能结果是，N-CoR可能提高靶基因启动子处ACTR的局部浓度。为支持这一假设，已证明N-CoR的存在可增强TRβ介导的转录激活。因此，有人提出，TRβ介导的激活和抑制以当前核受体作用模型未预测的方式紧密相连。
