SUMO modification regulates the transcriptional repressor function of aryl hydrocarbon receptor repressor.
The aryl hydrocarbon receptor (AhR) repressor (AhRR) inhibits the AhR activity. AhRR acts by competing with AhR for heterodimer formation with the AhR nuclear translocator (Arnt) and preventing the AhR.Arnt complex from binding the xenobiotic-responsive elements. Here, we report that AhRR has three evolutionarily conserved SUMOylation consensus sequences within its C-terminal repression domain and that Lys-542, Lys-583, and Lys-660 at the SUMOylation sites are modified by SUMO-1 in vivo. Arginine mutation of the three lysines results in a significant reduction of transcriptional repression activity. SUMOylation of the three lysine residues is important for the interaction between AhRR and ANKRA2, HDAC4, and HDAC5, which are important corepressors for AhRR. Arnt, a heterodimer partner for AhRR, markedly enhanced the SUMOylation of AhRR. AhRR, but not AhR, also significantly enhanced the SUMOylation of Arnt. The SUMOylation of both AhRR and Arnt is important for the efficient transcriptional repression activity of the AhRR/Arnt heterodimer.
Oshima
Motohiko
M
Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
Mimura
Junsei
J
Sekine
Hiroki
H
Okawa
Hiromi
H
Fujii-Kuriyama
Yoshiaki
Y
D000595:Amino Acid Sequence; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
D018336:Receptors, Aryl Hydrocarbon; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator