Receptor-interacting protein 140 binds c-Jun and inhibits estradiol-induced activator protein-1 activity by reversing glucocorticoid receptor-interacting protein 1 effect.
In the presence of estradiol, estrogen receptor-alpha (ERalpha) increases transcription triggered by activator protein-1 (AP-1). We have previously shown that induction is mediated by the direct interaction between c-Jun and ERalpha, which stabilizes a multiprotein complex containing the coactivator GRIP1 (glucocorticoid receptor interacting protein 1). The effect of receptor-interacting protein 140 (RIP140) in this regulation was assessed in the present study. We report that overexpression of RIP140 inhibits estradiol-induced AP-1-dependent transcription in a dose-dependent manner. Inhibition is not affected by trichostatin A, suggesting that histone deacetylase recruitment is not implicated. RIP140, which binds Jun proteins in pull-down assays and in intact cells, as shown by coimmunoprecipitation analysis and a mammalian one-hybrid system, participates in a multiprotein complex containing c-Jun and ERalpha. Moreover, the negative effect of RIP140 on AP-1-mediated transcription is relieved by GRIP1 overexpression and, conversely, RIP140 inhibits the stimulatory effect of GRIP1. The two cofactors compete for binding to c-Jun and ERalpha both in vitro and in intact cells, and GRIP1 interaction with both ERalpha and c-Jun is required for an efficient competition. These overall results suggest that the ratio between RIP140 and GRIP1 could determine, as proposed for hormone response element-mediated responses, the efficacy of estradiol in stimulating transcription of genes under AP-1 control.
Teyssier
Catherine
C
Institut National de la Santé et de la Recherche Médicale, Endocrinologie Moléculaire et Cellulaire des Cancers (U 540), 34090 Montpellier, France.
Belguise
Karine
K
Galtier
Florence
F
Cavailles
Vincent
V
Chalbos
Dany
D
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2; D000078723:Nuclear Receptor Interacting Protein 1; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; C498001:NCOA2 protein, human; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D000078723:Nuclear Receptor Interacting Protein 1; D016755:Proto-Oncogene Proteins c-jun; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C012589:trichostatin A; D004958:Estradiol