Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2.
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.
Youn
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Center for Cancer Research, Department of Biology, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sun
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Prywes
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Liu
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JO
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D019703:Calcineurin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D019169:Jurkat Cells; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D002147:Calmodulin; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D019703:Calcineurin; D002118:Calcium