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Akt inhibits the orphan nuclear receptor Nur77 and T-cell apoptosis

N Masuyama1, K Oishi, Y Mori

  • 1Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

The Journal of Biological Chemistry
|July 5, 2001
PubMed

Insights

The Akt protein inhibits Nur77, a factor involved in T-cell apoptosis, by blocking its DNA binding and promoting its association with 14-3-3. This Akt-mediated inhibition of Nur77 promotes cell survival.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Signaling

Background:

  • Akt is a key mediator of cell survival across various contexts.
  • The precise mechanisms of Akt in regulating apoptosis, especially in a cell-type-dependent manner, remain incompletely understood.
  • Nur77, a transcription factor, plays a role in T-cell receptor-mediated apoptosis.

Purpose of the Study:

  • To investigate the functional consequences of Akt phosphorylation on Nur77.
  • To elucidate the mechanism by which Akt antagonizes apoptosis through Nur77.
  • To determine if Akt acts as a negative regulator of Nur77 in T-cell apoptosis.

Main Methods:

  • Investigated the effect of Akt on Nur77 DNA binding activity.
  • Assessed the interaction between Akt and Nur77, focusing on phosphorylation sites and 14-3-3 association.
  • Evaluated the impact of Akt expression on Nur77-induced apoptosis in fibroblasts and T-cell hybridomas.

Main Results:

  • Akt was found to inhibit the DNA binding activity of Nur77 in a phosphorylation-dependent manner.
  • Akt expression stimulated the association of Nur77 with 14-3-3 proteins.
  • Akt suppressed Nur77-induced apoptosis in fibroblasts and activation-induced cell death in T-cell hybridomas.

Conclusions:

  • Akt directly antagonizes Nur77's function, thereby inhibiting apoptosis.
  • Akt acts as a negative regulator of Nur77, providing a mechanism for T-cell survival during T-cell receptor activation.
  • These findings contribute to understanding the complex interplay between Akt signaling and T-cell fate decisions.

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