Sci. STKE, 26 October 1999
Calcium and transcription factors Calcium and transcription factors: To Live or Let Die
The release of intracellular calcium (Ca2+) can trigger signals that lead to cell survival or to cell death; two reports illustrate how the same transcription factor, MEF2, which functions in the differentiation of skeletal muscle, can play different roles in the survival of neurons and T cells. During development of the mammalian brain, neurons that make proper synaptic connections and receive signals from other cells experience an increase in the intracellular Ca2+. This Ca2+ influx promotes cell survival or resistance to cell death. Mao et al. present evidence that MEF2 mediates the pro-survival effects of Ca2+ in cultured neuronal cells from the rat cerebral cortex. The increase in Ca2+ apparently causes activation of the p38 mitogen-activated protein kinase, which may directly phosphorylate and activate MEF2. Neuronal survival thus appears to be modulated through transcriptional regulation by MEF2, as well as through posttranslational changes in components of the cell death machinery. Activation of mature T cells eventually leads to their demise. It is thought that expression of the Nur77 orphan steroid receptor (whose transcription is dependent on Ca2+), the phosphatase calcineurin, and the transcription factor MEF2, mediates this apoptosis. Youn et al. have begun to elucidate the regulation of Nur77 expression and T cell apoptosis. Endogenous MEF2 is bound by Cabin 1, an inhibitor of calcineurin. When intracellular Ca2+ increases, calmodulin competes for binding to Cabin 1 at the same site as MEF2 and forces the release of MEF2, which makes it available for assembly into a transcriptional complex.
Mao, Z., Bonni, A., Xia, F., Nadal-Vicens, M., and Greenberg. M.E. (1999) Neuronal activity-dependent cell survival dediated by transcription factor MEF2. Science 286: 785 - 790. [Abstract] [Full Text]
Citation: Calcium and transcription factors: To Live or Let Die. Sci. STKE 1999, tw8 (1999).
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