Publication Date:
1999-10-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Youn, H D -- Sun, L -- Prywes, R -- Liu, J O -- GM55783/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):790-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Department of Biology, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10531067" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing
;
*Apoptosis
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Calcineurin/chemistry/genetics/metabolism/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/genetics/*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/genetics/metabolism/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/*metabolism
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Transcription Factors/chemistry/genetics/*metabolism
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Transcription, Genetic
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Two-Hybrid System Techniques
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
