Apoptosis of T Cells Mediated by Ca2+-Induced Release of the Transcription Factor MEF2

HD Youn, L Sun, R Prywes, JO Liu - Science, 1999 - science.org
HD Youn, L Sun, R Prywes, JO Liu
Science, 1999science.org
T cell receptor (TCR)–induced apoptosis of thymocytes is mediated by calcium-dependent
expression of the steroid receptors Nur77 and Nor1. Nur77 expression is controlled by the
transcription factor myocyte enhancer factor 2 (MEF2), but how MEF2 is activated by calcium
signaling is still obscure. Cabin1, a calcineurin inhibitor, was found to regulate MEF2. MEF2
was normally sequestered by Cabin1 in a transcriptionally inactive state. TCR engagement
led to an increase in intracellular calcium concentration and the dissociation of MEF2 from …
T cell receptor (TCR)–induced apoptosis of thymocytes is mediated by calcium-dependent expression of the steroid receptors Nur77 and Nor1. Nur77 expression is controlled by the transcription factor myocyte enhancer factor 2 (MEF2), but how MEF2 is activated by calcium signaling is still obscure. Cabin1, a calcineurin inhibitor, was found to regulate MEF2. MEF2 was normally sequestered by Cabin1 in a transcriptionally inactive state. TCR engagement led to an increase in intracellular calcium concentration and the dissociation of MEF2 from Cabin1, as a result of competitive binding of activated calmodulin to Cabin1. The interplay between Cabin1, MEF2, and calmodulin defines a distinct signaling pathway from the TCR to the Nur77 promoter during T cell apoptosis.
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