Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling

Cell. 1999 Jan 8;96(1):121-30. doi: 10.1016/s0092-8674(00)80965-4.

Abstract

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.

MeSH terms

  • CREB-Binding Protein
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Line, Transformed
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Humans
  • Interferon-gamma / immunology*
  • Interferon-gamma / pharmacology
  • Interleukin-2 / immunology*
  • Interleukin-2 / pharmacology
  • Intracellular Signaling Peptides and Proteins*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Milk Proteins*
  • Nuclear Proteins / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Milk Proteins
  • NMI protein, human
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • STAT5 Transcription Factor
  • STAT5B protein, human
  • Trans-Activators
  • Interferon-gamma
  • CREB-Binding Protein
  • CREBBP protein, human