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SUMOylation of AhR modulates its activity and stability through inhibiting its ubiquitination
Author(s) -
Xing Xinrong,
Bi Hailian,
Chang Alan K.,
Zang MingXi,
Wang Miao,
Ao Xiang,
Li Shen,
Pan Hongming,
Guo Qianping,
Wu Huijian
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24092
Subject(s) - sumo protein , transactivation , aryl hydrocarbon receptor , transcription factor , ubiquitin , aryl hydrocarbon receptor nuclear translocator , chemistry , microbiology and biotechnology , transcription (linguistics) , biology , biochemistry , gene , linguistics , philosophy
Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix–loop–helix (bHLH) Per‐Arnt‐Sim homology domain (PAS) family. AhR can be activated by 2, 3, 7, 8‐tetrachlorodibenzo‐ p ‐dioxin (2, 3, 7, 8‐TCDD) and once activated, it promotes the abnormal expression of cytochrome P450, leading to several diseases, including cancer. In this study, we showed that AhR is subjected to post‐translational modification by SUMOylation and this modification could be reversed by SENP1. Two SUMOylation sites were identified, one in the bHLH domain (K63) and the other in the TAD domain (K510) of AhR. Substitution of either K63 or K510 with arginine resulted in reduced SUMOylation for AhR. Treatment of MCF‐7 cells with TCDD led to a reduced level of SUMOylated AhR in a time‐dependent manner, and this occurred mainly in the nucleus. SUMOylation of AhR enhanced its stability through inhibiting its ubiquitination. Moreover, SUMOylation also repressed the transactivation activity of AhR and this could be reversed by TCDD. These results suggested that SUMOylation of AhR might play an important role in the regulation of its function, and TCDD may activate the transcriptional activity of AhR through downregulating its SUMOylation. J. Cell. Physiol. 227: 3812–3819, 2012. © 2012 Wiley Periodicals, Inc.