title: Coactivator recruitment of AhR/ARNT1.
abstract: A common feature of nuclear receptors (NRs) is the transformation of external cell signals into specific transcriptions of the signal molecule. Signal molecules function as ligands for NRs and, after their uptake, activated NRs form homo- or heterodimers at promoter recognition sequences of the specific genes in the nucleus. Another common feature of NRs is their dependence on coactivators, which bridge the basic transcriptional machinery and other cofactors to the target genes, in order to initiate transcription and to unwind histone-bound DNA for exposing additional promoter recognition sites via their histone acetyltransferase (HAT) function. In this review, we focus on our recent findings related to the recruitment of steroid receptor coactivator 1 (SRC1/NCoA1) by the estrogen receptor-α (ERα) and by the arylhydrocarbon receptor/arylhydrocarbon receptor nuclear translocator 1 (AhR/ARNT1) complex. We also describe the extension of our previously published findings regarding the binding between ARNT1.1 exon16 and SRC1e exon 21, via in silico analyses of androgen receptor (AR) NH2-carboxyl-terminal interactions, the results of which were verified by in vitro experiments. Based on these data, we suggest a newly derived tentative binding site of nuclear coactivator 2/glucocorticoid receptor interacting protein-1/transcriptional intermediary factor 2 (NCOA-2/ GRIP-1/TIF-2) for ARNT1.1 exon 16. Furthermore, results obtained by immunoprecipitation have revealed a second leucine-rich binding site for hARNT1.1 exon 16 in SRC1e exon 21 (LSSTDLL). Finally, we discuss the role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an endocrine disruptor for estrogen related transcription.
authors.affiliation: Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. alexanderendler@msn.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Endler
authors.affiliation: Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. LiCHEN@biomed-sh.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. shibasaki-ft@igakuken.or.jp.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Shibasaki
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2 / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D052244:Endocrine Disruptors; C491310:GRIP1 protein, human; D009419:Nerve Tissue Proteins; D051958:Nuclear Receptor Coactivator 2; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator