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

It is not known how the protein Bcl-2 inhibits cell death induced by calcium signalling and growth-factor withdrawal. 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 activity. 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.
Mesh Terms:
Amino Acid Sequence, Animals, B-Lymphocytes, Binding Sites, Biological Transport, Calcineurin, Calmodulin-Binding Proteins, Cell Line, Cell Nucleus, Consensus Sequence, Cricetinae, DNA-Binding Proteins, Humans, Intracellular Membranes, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Proteins, Phosphoprotein Phosphatases, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Sequence Alignment, Signal Transduction, T-Lymphocytes, Transcription Factors, bcl-2-Associated X Protein
Nature
Date: Apr. 17, 1997
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