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Nuclear accumulation of interferon gamma

T Bader1, J Weitzerbin

  • 1Unité 365 Institut National de la Santé et de la Recherche Médicale, Interférons et Cytokines, Institut Curie, Paris, France.

Proceedings of the National Academy of Sciences of the United States of America
|December 6, 1994
PubMed

Insights

Interferon gamma (IFN-gamma) has a nuclear localization signal, enabling its entry into the cell nucleus. This nuclear translocation, even with its receptor, suggests a role in IFN-gamma signal transduction.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Interferon gamma (IFN-gamma) is a cytokine crucial for immune responses.
  • The precise mechanisms of IFN-gamma signal transduction are not fully understood.
  • Nuclear localization signals (NLS) are sequences that direct proteins to the nucleus.

Purpose of the Study:

  • To investigate the potential nuclear localization of IFN-gamma.
  • To identify functional nuclear localization signals within the IFN-gamma amino acid sequence.
  • To explore the role of nuclear translocation in IFN-gamma signaling.

Main Methods:

  • Analysis of IFN-gamma amino acid sequence for conserved motifs.
  • Autoradiography and indirect immunofluorescence to track IFN-gamma localization in L1210 cells.
  • Use of murine and human IFN-gamma and its receptor in transfected cells.
  • Chemical crosslinking of IFN-gamma to its receptor.

Main Results:

  • Two conserved basic amino acid clusters resembling NLS were identified in IFN-gamma.
  • Murine IFN-gamma accumulated in the nucleus of L1210 cells in a time- and temperature-dependent manner.
  • Human IFN-gamma was transiently nuclear in transfected cells expressing the human receptor.
  • IFN-gamma, crosslinked to its receptor, was still translocated to the nucleus.

Conclusions:

  • The identified bipartite sequence functions as a nuclear localization signal for IFN-gamma.
  • IFN-gamma can be actively transported into the nucleus, potentially as a receptor-ligand complex.
  • Nuclear targeting of IFN-gamma may play a role in its overall signal transduction pathway.

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