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Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2

Nature volume 386, pages 728–731 (1997)Cite this article

Abstract

It is not known how the protein Bcl-2 inhibits cell death induced by calcium signalling and growth-factor withdrawal1–3. Here we report that Bcl-2 forms a tight complex with calcineurin, resulting in the targeting of calcineurin to Bcl-2 sites on cytoplasmic membranes, and show that this interaction is dependent on the BH4 domain of Bcl-2. Calcineurin bound to Bcl-2 is an active phosphatase but is unable to promote the nuclear translocation of NF-AT, a transcription-factor required for induction of interleukin-2 expression, suggesting a mechanism by which Bcl-2 suppresses NF-AT activity4. We also show that Bax, a pro-apoptotic member of the Bcl-2 family, interferes with interactions between calcineurin and Bcl-2. We propose that the ability of Bcl-2 to block NF-AT signalling is due to the sequestering of active calcineurin to the same domain of Bcl-2 which associates with Rad-1 (ref. 5), and that calcineurin may act in Bcl-2-regulated functions.

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Author notes

  1. Eisaku Kondo and Tadaatsu Akagi: Second Department of Pathology, Okayama University Medical School, 2-5-1 Shikata-Cho, Okayama 700, Japan

Authors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Futoshi Shibasaki, Eisaku Kondo, Tadaatsu Akagi & Frank McKeon

Authors
  1. Futoshi Shibasaki
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  2. Eisaku Kondo
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  3. Tadaatsu Akagi
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  4. Frank McKeon
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Shibasaki, F., Kondo, E., Akagi, T. et al. Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2. Nature 386, 728–731 (1997). https://doi.org/10.1038/386728a0

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