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 expression in T lymphocytes and cardiomyocytes. We show here that the transcriptional co-activators CBP/p300 bind to and control the activity of the inducible N-terminal transactivation domain of NF-ATc, TAD-A. Similar to the N terminal transactivation domain of c-Jun, TAD-A is inducibly phosphorylated, but this phosphorylation is dispensable for the interaction with CBP/p300. Constitutive active versions of c-Raf and Rac synergistically enhance the CBP/p300-mediated increase of TAD-A activity, indicating the important role CBP/p300 plays in the integration of T cell activation signals. Since a mutation 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 control the NF-AT-dependent transcription in T cells.
Avots
A
A
Department of Molecular Pathology, Institute of Pathology, University of Wuerzburg, Germany.
Buttmann
M
M
Chuvpilo
S
S
Escher
C
C
Smola
U
U
Bannister
A J
AJ
Rapp
U R
UR
Kouzarides
T
T
Serfling
E
E
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009687:Nuclear Proteins / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology; D020744:rac GTP-Binding Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins