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Related Experiment Videos

Functional cooperation between JunD and NF-kappaB in rat hepatocytes.

M Rahmani1, P Péron, J Weitzman

  • 1Laboratoire de Biologie cellulaire, INSERM U 327, Faculté de Médecine Xavier Bichat et Université Paris 7 Denis Diderot, Paris, France.

Oncogene
|August 30, 2001
PubMed
Summary

Activating protein 1 (AP-1) and nuclear factor kappa B (NF-kappaB) are key in liver regeneration. This study shows JunD, a component of AP-1, functionally cooperates with NF-kappaB during this process.

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Area of Science:

  • Hepatology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Activating protein 1 (AP-1) and nuclear factor kappa B (NF-kappaB) are transcription factors rapidly activated during liver regeneration.
  • The functional relationship between AP-1 and NF-kappaB during liver regeneration is not well understood.

Purpose of the Study:

  • To investigate the functional implications of parallel AP-1 and NF-kappaB activation during liver regeneration.
  • To determine if AP-1 influences NF-kappaB activity in hepatocytes.

Main Methods:

  • Hepatocytes were stimulated with epidermal growth factor, hepatocyte growth factor, and tumor necrosis factor alpha.
  • AP-1 and NF-kappaB binding activity was assessed using electrophoretic mobility shift assays.
  • NF-kappaB-dependent transcription was measured using reporter assays.

Related Experiment Videos

  • Dominant-negative AP-1 mutant (TAM67) and JunD overexpression were used to assess functional cooperation.
  • NF-kappaB transactivation was compared in hepatocytes from JunD knockout and wild-type mice.

    • Main Results:

    • Epidermal growth factor, hepatocyte growth factor, and tumor necrosis factor alpha increased AP-1 and NF-kappaB binding and activated NF-kappaB-dependent transcription.
    • Inactivation of AP-1 by TAM67 significantly inhibited basal and cytokine-induced NF-kappaB transactivation.
    • Overexpression of JunD, but not other Jun or Fos proteins, threefold increased NF-kappaB transactivation.
    • Functional cooperation between JunD and p65 (a subunit of NF-kappaB) was demonstrated.
    • NF-kappaB transactivation was reduced in hepatocytes from JunD knockout mice compared to wild-type mice.

    Conclusions:

    • AP-1 and NF-kappaB signaling pathways functionally cooperate during liver regeneration.
    • JunD, a major component of AP-1, plays a crucial role in regulating NF-kappaB transactivation in hepatocytes.
    • These findings elucidate a key molecular mechanism underlying liver regenerative processes.