Selective suppression of the human aryl hydrocarbon receptor function can be mediated through binding interference at the C-terminal half of the receptor.
Selective suppression of the human aryl hydrocarbon receptor function can be mediated through binding interference at the C-terminal half of the receptor.
复制标题
人类芳烃受体功能的选择性抑制可以通过受体 C 端一半的结合干扰来介导。
DOI：
10.1016/j.bcp.2016.03.004
复制
发表时间：
2016
影响因子：
5.8
通讯作者：
Chan,WilliamK
中科院分区：
文献类型：
--
作者：
Ren,Lina;Thompson,JohnD;Cheung,Michael;Ngo,Katherine;Sung,Sarah;Leong,Scott;Chan,WilliamK
The human aryl hydrocarbon receptor is a cytosolic signaling molecule which affects immune response and aberrant cell growth. Canonical signaling of the receptor requires the recruitment of coactivators to the promoter region to remodel local chromatin structure. We predicted that interference of this recruitment would block the aryl hydrocarbon receptor function. To prove that, we employed phage display to identify nine peptides of twelve-amino-acid in length which target the C-terminal half of the human aryl hydrocarbon receptor, including the region where coactivators bind. Eight 12mer peptides, in the form of GFP fusion, suppressed the ligand-dependent transcription of six AHR target genes (cyp1a1,cyp1a2,cyp1b1,ugt1a1,nqo1, andahrr) in different patterns in Hep3B cells, whereas the AHR antagonist CH-223191 suppressed all these target genes similarly. Three of the 12mer peptides (namely 11-3, 1-7, and 7-3) suppressed the 3MC-induced, CYP1A1-dependent EROD activity and the ROS production caused by benzo[a]pyrene. These 12mer peptides suppressed the AHR function synergistically with CH-223191. In conclusion, we provide evidence that targeting the C-terminal half of the human aryl hydrocarbon receptor is a viable, new approach to selectively block the receptor function.
