title: Estrogen receptor pathways to AP-1.
abstract: Estrogen receptor (ER) binds to estrogen response elements in target genes and recruits a coactivator complex of CBP-pl60 that mediates stimulation of transcription. ER also activates transcription at AP-1 sites that bind the Jun/Fos transcription factors, but not ER. We review the evidence regarding mechanisms whereby ER increases the activity of Jun/Fos and propose two pathways of ER action depending on the ER (alpha or beta) and on the ligand. We propose that estrogen-ERalpha complexes use their activation functions (AF-1 and AF-2) to bind to the p 160 component of the coactivator complex recruited by Jun/Fos and trigger the coactivator to a higher state of activity. We propose that selective estrogen receptor modulator (SERM) complexes with ERbeta and with truncated ERalpha derivatives use their DNA binding domain to titrate histone deacetylase (HDAC)-repressor complexes away from the Jun/Fos coactivator complex, thereby allowing unfettered activity of the coactivators. Finally, we consider the possible physiological significance of ER action at AP-1 sites.
authors.affiliation: Metabolic Research Unit, 1119 HSW, University of California, 3rd and Parnassus, 94143-0540, San Francisco, CA, USA. kushner@itsa.ucsf.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Kushner
authors.forename: D A
authors.initials: DA
authors.lastname: Agard
authors.forename: G L
authors.initials: GL
authors.lastname: Greene
authors.forename: T S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: A K
authors.initials: AK
authors.lastname: Shiau
authors.forename: R M
authors.initials: RM
authors.lastname: Uht
authors.forename: P
authors.initials: P
authors.lastname: Webb
mesh_terms: D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen; D012097:Repressor Proteins; D020845:Selective Estrogen Receptor Modulators; D018808:Transcription Factor AP-1