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

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