Controlling Nuclear Jaks and Stats for Specific Gene Activation by Ifn γ and Other Cytokines: A Possible Steroid-like

Howard M Johnson1, Ezra Noon-Song, Chulbul M Ahmed

  • 1Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.

Journal of Clinical & Cellular Immunology
|August 28, 2012
PubMed

Insights

The JAK/STAT pathway

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Epigenetics

Background:

  • The JAK/STAT signaling pathway regulates gene expression in response to cytokines.
  • Specificity in this pathway is not well understood, despite limited numbers of Janus kinases (JAKs) and Signal transducer and activator of transcription (STATs).
  • The classical model posits limited roles for ligands, receptors, and JAKs after initial signaling events.

Purpose of the Study:

  • To elucidate the mechanism of specific gene activation mediated by the JAK/STAT pathway.
  • To investigate the roles of ligand, receptor, and JAKs in nuclear events of gene activation, particularly for gamma interferon (IFNγ).

Main Methods:

  • Focus on gamma interferon (IFNγ) signaling.
  • Investigated the involvement of ligand, receptor, and activated JAKs in nuclear events.
  • Characterized the function of the IFNGR1 receptor subunit and JAKs in gene activation and epigenetic modifications.

Main Results:

  • Demonstrated that ligand, receptor, and activated JAKs participate in nuclear events for specific gene activation.
  • Identified the receptor subunit IFNGR1 as a transcription/cotranscription factor.
  • Showed JAKs are crucial for epigenetic events essential for specific gene activation.

Conclusions:

  • The classical JAK/STAT signaling model is incomplete.
  • Receptor subunits and JAKs play active roles in the nucleus during gene activation.
  • This revised model has implications for understanding gene regulation in cancer and stem cell differentiation.

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