Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Apoptosis*
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Calcineurin / chemistry
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Calcineurin / genetics
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Calcineurin / metabolism
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Calcineurin / pharmacology
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Calcium / metabolism
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Calcium Signaling*
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Calmodulin / metabolism
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Cell Line
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression
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Genes, Reporter
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Humans
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Jurkat Cells
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MEF2 Transcription Factors
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Myogenic Regulatory Factors
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Phosphoproteins / pharmacology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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T-Lymphocytes / cytology*
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T-Lymphocytes / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
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Two-Hybrid System Techniques
Substances
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Adaptor Proteins, Signal Transducing
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CABIN1 protein, human
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Calmodulin
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DNA-Binding Proteins
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MEF2 Transcription Factors
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Myogenic Regulatory Factors
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NR4A1 protein, human
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Phosphoproteins
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Receptors, Antigen, T-Cell
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Transcription Factors
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Calcineurin
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Calcium