Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling.
Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen, we identified the association of Nmi, a protein of unknown function previously reported as an N-Myc interactor. We further show that Nmi interacts with all STATs except Stat2. We evaluated two cytokine systems, IL-2 and IFNgamma, and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines. Interestingly, Nmi lacks an intrinsic transcriptional activation domain; instead, Nmi enhances the association of CBP/p300 coactivator proteins with Stat1 and Stat5, and together with CBP/p300 can augment IL-2- and IFNgamma-dependent transcription. Therefore, our data not only reveal that Nmi can potentiate STAT-dependent transcription, but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors.
Zhu
M
M
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA.
John
S
S
Berg
M
M
Leonard
W J
WJ
D050882:CREB-Binding Protein; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic