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Science 286 (5440): 790-793

Copyright © 1999 by the American Association for the Advancement of Science

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

Hong-Duk Youn, 1 Luo Sun, 1 Ron Prywes, 4 Jun O. Liu 123*

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.

1 Center for Cancer Research,
2 Department of Biology,
3 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4 Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
*   To whom correspondence should be addressed. E-mail: Junliu{at}

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