The nuclear-receptor interacting protein (RIP) 140 binds to the human glucocorticoid receptor and modulates hormone-dependent transactivation.
The glucocorticoid receptor (GR) regulates target gene expression in response to corticosteroid hormones. We have investigated the mechanism of transcriptional activation by the GR by studying the role of the receptor interacting protein RIP140. Both in vivo and in vitro protein-protein interaction assays revealed a ligand-dependent interaction between the GR and RIP140. The ligand binding domain of the GR was sufficient for this interaction, while both the N- and C-terminal regions of RIP140 bound to the receptor. In a yeast transactivation assay RIP140 and SRC-1, a member of the steroid receptor coactivator family of proteins, both enhanced the transactivation activity of a GR protein (GRA-1) in which the potent N-terminal tau1 transactivation domain has been deleted. In contrast, in COS-7 cells increasing amounts of RIP140 significantly inhibited GRdeltatau1 function. In cotransfection studies in COS-7 cells, RIP140 also inhibited receptor activity in presence of both SRC-1 and the coactivator protein CBP together. Thus, in yeast cells a stimulation of receptor activity was observed, while in mammalian cells RIP140 repressed GR function. Taken together, these data suggest that, (1) RIP140 is a target protein for the GR and (2) RIP140 can modulate the transactivation activity of the receptor.
Windahl
S H
SH
Department of Biosciences, Karolinska Institute, Huddinge, Sweden. sara.windahl@cbt.ki.se
Treuter
E
E
Ford
J
J
Zilliacus
J
J
Gustafsson
J A
JA
McEwan
I J
IJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D000078723:Nuclear Receptor Interacting Protein 1; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D008024:Ligands; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1