Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2

Science. 1999 Oct 22;286(5440):790-3. doi: 10.1126/science.286.5440.790.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Apoptosis*
  • Calcineurin / chemistry
  • Calcineurin / genetics
  • Calcineurin / metabolism
  • Calcineurin / pharmacology
  • Calcium / metabolism
  • Calcium Signaling*
  • Calmodulin / metabolism
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Jurkat Cells
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphoproteins / pharmacology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • CABIN1 protein, human
  • Calmodulin
  • DNA-Binding Proteins
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Calcineurin
  • Calcium