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NF-AT activation requires suppression of Crm1-dependent export by calcineurin

J Zhu1, F McKeon

  • 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Nature
|March 27, 1999
PubMed

Insights

Nuclear import of NF-AT transcription factors requires calcineurin. Calcineurin also prevents NF-AT export, ensuring T-cell activation by regulating nuclear transport.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Nuclear import of NF-AT transcription factors is crucial for T-cell activation.
  • This process is mediated by the calcium-activated phosphatase calcineurin, which unmasks nuclear-location signals.

Purpose of the Study:

  • To investigate the regulation of NF-AT transcription factors during T-cell activation.
  • To elucidate the role of calcineurin in controlling NF-AT nuclear transport and gene activation.

Main Methods:

  • Studied the nuclear import and export dynamics of NF-AT transcription factors.
  • Investigated the interaction between NF-AT, calcineurin, and the exportin Crm1.
  • Examined the non-catalytic mechanisms of calcineurin in regulating NF-AT shuttling.

Main Results:

  • Nuclear import of NF-AT is insufficient for target gene activation due to futile cycling.
  • NF-ATs are exported by Crm1, a process suppressed by calcineurin.
  • Calcineurin inhibits Crm1-mediated export through a non-catalytic mechanism, masking nuclear export signals.

Conclusions:

  • Calcineurin's non-catalytic function is critical for suppressing futile NF-AT cycling and enabling T-cell activation.
  • The competition between calcineurin and Crm1 binding sites on NF-AT confers calcium sensitivity to transcription factor dynamics.
  • This regulatory balance may extend to other transcription factors involved in nuclear transport.

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