A stimulus-specific role for CREB-binding protein (CBP) in T cell receptor-activated tumor necrosis factor alpha gene expression.

Published

Journal Article

The cAMP response element binding protein (CREB)-binding protein (CBP)/p300 family of coactivator proteins regulates gene transcription through the integration of multiple signal transduction pathways. Here, we show that induction of tumor necrosis factor alpha (TNF-alpha) gene expression in T cells stimulated by engagement of the T cell receptor (TCR) or by virus infection requires CBP/p300. Strikingly, in mice lacking one copy of the CBP gene, TNF-alpha gene induction by TCR activation is inhibited, whereas virus induction of the TNF-alpha gene is not affected. Consistent with these findings, the transcriptional activity of CBP is strongly potentiated by TCR activation but not by virus infection of T cells. Thus, CBP gene dosage and transcriptional activity are critical in TCR-dependent TNF-alpha gene expression, demonstrating a stimulus-specific requirement for CBP in the regulation of a specific gene.

Full Text

Duke Authors

Cited Authors

  • Falvo, JV; Brinkman, BM; Tsytsykova, AV; Tsai, EY; Yao, TP; Kung, AL; Goldfeld, AE

Published Date

  • April 11, 2000

Published In

Volume / Issue

  • 97 / 8

Start / End Page

  • 3925 - 3929

PubMed ID

  • 10760264

Pubmed Central ID

  • 10760264

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.97.8.3925

Language

  • eng

Conference Location

  • United States