title: SUMOylation of AhR modulates its activity and stability through inhibiting its ubiquitination.
abstract: 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.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Xing
authors.forename: Hailian
authors.initials: H
authors.lastname: Bi
authors.forename: Alan K
authors.initials: AK
authors.lastname: Chang
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Zang
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.forename: Qianping
authors.initials: Q
authors.lastname: Guo
authors.forename: Huijian
authors.initials: H
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D017434:Protein Structure, Tertiary; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D025842:SUMO-1 Protein