Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis
AUTOR(ES)
Youn, Hong-Duk
FONTE
Oxford University Press
RESUMO
T-cell antigen receptor (TCR)-induced thymocyte apoptosis is mediated by calcium-dependent signal transduction pathways leading to the transcriptional activation of members of the Nur77 family. The major calcium- and calcineurin-responsive elements in the Nur77 promoter are binding sites for myocyte enhancer factor-2 (MEF2). It has been shown that nuclear factor of activated T cells (NFAT) interacts with MEF2D and enhances its transcriptional activity, offering a plausible mechanism of activation of MEF2D by calcineurin. We report here that NFATp synergizes with MEF2D to recruit the coactivator p300 for the transcription of Nur77. Surprisingly, the enhancement of transcriptional activity of MEF2D by NFATp does not require its DNA-binding activity, suggesting that NFATp acts as a coactivator for MEF2D. Transient co-expression of p300, MEF2D, NFATp and constitutively active calcineurin is sufficient to recapitulate TCR signaling for the selective induction of the endogenous Nur77 gene. These results implicate NFAT as an important mediator of T-cell apoptosis and suggest that NFAT is capable of integrating the calcineurin signaling pathway and other pathways through direct protein–protein interaction with other transcription factors.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=302027Documentos Relacionados
- Recruitment of p300 by C/EBPβ triggers phosphorylation of p300 and modulates coactivator activity
- Acetylation of Nucleosomal Histones by p300 Facilitates Transcriptionfrom Tax-Responsive Human T-Cell Leukemia Virus Type 1Chromatin Template
- Polyomavirus Large T Antigen Binds the Transcriptional Coactivator Protein p300
- Acetylation of Nucleosomal Histones by p300 Facilitates Transcription from Tax-Responsive Human T-Cell Leukemia Virus Type 1 Chromatin Template
- Regulation of β-catenin transformation by the p300 transcriptional coactivator