The aryl hydrocarbon receptor nuclear translocator-interacting protein 2 suppresses the estrogen receptor signaling via an Arnt-dependent mechanism.
We explored whether modulation of the estrogen receptor (ER) signaling is possible through an aryl hydrocarbon receptor nuclear translocator (Arnt)-dependent mechanism. We utilized the Arnt-interacting protein 2 (Ainp2) to examine whether the presence of Ainp2 in MCF-7 cells would interfere with the Arnt-mediated ER signaling. We found that Arnt increased the 17 beta-estradiol (E2)-dependent luciferase activity and Ainp2 significantly suppressed this Arnt-mediated luciferase activity. Ainp2 significantly suppressed 25% of the E2- and Arnt-dependent up-regulation of the GREB1 message. No suppression of the ER target gene expression by Ainp2 was detected in Arnt-knockdown MCF-7 cells and in Arnt-independent ER signaling. Although Ainp2 did not interact with ER alpha and ER beta, it suppressed the ER alpha::Arnt interaction and reduced the E2-driven recruitment of Arnt to the GREB1 promoter. We concluded that Ainp2 suppresses the ER signaling by not allowing Arnt to participate in the ER-dependent, Arnt-mediated activation of gene transcription.
Li
Yanjie
Y
Department of Pharmaceutics and Medicinal Chemistry, University of the Pacific, Stockton, CA 95211, USA.
Li
Yi
Y
Zhang
Tianmin
T
Chan
William K
WK
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; C103265:aryl hydrocarbon receptor-interacting protein; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004958:Estradiol