CBP/p300 integrates Raf/Rac-signaling pathways in the transcriptional induction of NF-ATc during T cell activation

NF-ATc, an inducibly expressed transcription factor, controls gene expressi on in T lymphocytes and cardiomyocytes. We show here that the transcription al coactivators CBP/p300 bind to and control the activity of the inducible N-terminal transactivation domain of NF-ATc, TAD-A. Similar to the N termin al transactivation domain of c-Jun, TAD-A is inducibly phosphorylated, but this phosphorylation is dispensable for the interaction with CBP/p300. Cons titutive active versions of c-Raf and Rac synergistically enhance the CBP/p 300-mediated increase of TAD-A activity, indicating the important role CBP/ p300 plays in the integration of T cell activation signals. Since a mutatio n of CBP abolishing HAT activity is almost as active as wild-type CBP in T cells, functions of CBP/p300 other than histone acetylation appear to contr ol the NF-AT-dependent transcription in T cells.