The nuclear isoform of the LIM domain protein Trip6 integrates activating and repressing signals at the promoter-bound glucocorticoid receptor.
Trip6 belongs to a family of cytosolic LIM domain proteins involved in cell adhesion and migration. Recent findings show that these proteins also regulate transcription. We have previously reported that nTrip6, a nuclear isoform of Trip6, acts as a co-activator for AP-1 and NF-kappaB transcription factors. Here we report that nTrip6 is an essential regulator of glucocorticoid receptor (GR) transcriptional activity. nTrip6 is recruited to GR-bound promoters through an interaction with GR, and increases GR-mediated transcription. nTrip6 is also essential for the transrepression of GR by NF-kappaB and AP-1. The interaction of nTrip6 with NF-kappaB and AP-1 at a GR-bound promoter is required for the repression. Thus, nTrip6 serves as the molecular mediator of the crosstalk between nuclear receptors and other transcription factors in that it assembles these factors at promoters. Our results reveal an essential role for LIM domain proteins in the integration of positive and negative signals at target promoters.
Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Karlsruhe, Germany.
Markus E
ME
Diefenbacher
Margarethe
M
Litfin
Peter
P
Herrlich
Olivier
O
Kassel
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; D016328:NF-kappa B; C092282:PSMC5 protein, human; D020033:Protein Isoforms; D016760:Proto-Oncogene Proteins c-fos; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities