caa a22 4500 378861697 CHVBK 20180305123348.0 cr unu---uuuuu 161128e20030101xx s 000 0 eng 10.1351/pac200375111819 doi (NATIONALLICENCE)gruyter-10.1351/pac200375111819 Transcriptional roles of AhR in expression of biological effects induced by endocrine disruptors [Elektronische Daten] [Yoshiaki Fujii-Kuriyama, J. Mimura] 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of most toxic man-made chemicals, binds arylhydrocarbon receptor (AhR or dioxin receptor), whose endogenous ligand remains unknown, with an extremely high affinity and expresses pleiotropic biological effects. From analysis of the primary structures, AhR belongs to a distinct group of a super-gene family from that of nuclear receptors. PCB, 3-methylcholanthrene, and benzo(a)pyrene are also ligands to the AhR, and these polycyclic aromatic chemicals are considered to display pleiotropic biological effects such as induction of a variety of drug-metabolizing enzymes, teratogenesis, tumor promotion, immunodeficiency due to thymic involution, and liver damage. Generation of the AhR-deficient mice by gene knock-out technology revealed that these biological effects described are mediated by AhR, because AhR(-/-) mice lost susceptibility to these effects by TCDD and benzo(a) pyrene. It has recently been revealed that AhR is also involved in reproduction of female mice. Although the detailed mechanisms of involvement of AhR in exerting these effects are not always clarified, AhR is generally considered to function as a transcription factor, which activates the expression of genes by binding directly the XRE sequence in their promoter in a heterodimer form with Arnt. From analysis of DNA transfection and GST pull-down assays, it is revealed that AhR and Arnt interact with various coactivators such as RIP140, SRC-1/NcoA, and CBP/p300 to transmit their transactivation activity to general transcription factors (GTFs). AhR has also been shown to interact with various regulatory factors including Rb, NF-κB, and SP1, resulting in mutual inhibition or synergistic enhancement of their activities depending on the mode of localization of their cognate binding sequences in the target genes. Agonistic and antagonistic properties of various ligands to AhR also are discussed. © 2013 Walter de Gruyter GmbH, Berlin/Boston Fujii-Kuriyama Yoshiaki Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tennoudai, 1-1-1, Tsukuba, Ibaraki, 305-8577, Japan aut Mimura J. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation aut Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 1819-1826 0033-4545 75:11-12<1819 2003 75 pac https://doi.org/10.1351/pac200375111819 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200375111819 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fujii-Kuriyama Yoshiaki Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tennoudai, 1-1-1, Tsukuba, Ibaraki, 305-8577, Japan aut NATIONALLICENCE 700 1- Mimura J. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation aut NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 1819-1826 0033-4545 75:11-12<1819 2003 75 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter