title: Repressive domain of unliganded human estrogen receptor alpha associates with Hsc70.
abstract: Estrogen receptor (ER) is a hormone-inducible transcription factor as a member of the nuclear receptor gene superfamily. Unliganded ER is transcriptionally silent and capable of DNA binding; however, it is unable to suppress the basal activity of the target gene promoters, unlike non-steroid hormone receptors that associate with corepressors in the absence of their cognate ligands. To study the molecular basis of how unliganded human ERalpha is maintained silent in gene regulation upon the target gene promoters, we biochemically searched interactants for hERalpha, and identified heat shock protein 70 (Hsc70). Hsc70 appeared to associate with the N-terminal hormone binding E domain, that also turned out a transcriptionally repressive domain. Competitive association of Hsc70 with a best known coactivator p300 was observed. Thus, these findings suggest that Hsc70 associates with unliganded hERalpha, and thereby deters hERalpha from recruiting transcriptional coregulators, presumably as a component of chaperone complexes.
authors.affiliation: The Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ogawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Oishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mezaki
authors.forename: Madoka
authors.initials: M
authors.lastname: Kouzu-Fujita
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsuyama
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakagomi
authors.forename: Eri
authors.initials: E
authors.lastname: Mori
authors.forename: Emi
authors.initials: E
authors.lastname: Murayama
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection
chemical_list: D047628:Estrogen Receptor alpha; D018840:HSP70 Heat-Shock Proteins; D008024:Ligands; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins