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 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.