Phosphorylation by p44 MAP Kinase/ERK1 stimulates CBP histone acetyl transferase activity in vitro.
The transcriptional coactivator CBP displays an intrinsic histone acetyl transferase (HAT) activity which seems to participate in transcriptional activation through the destabilization of nucleosome structure. CBP is involved in the activity of several transcription factors that are nuclear endpoints of intracellular signal transduction pathways. In some instances, the transcription factors are phosphorylated upon cell activation, which induces their interaction with CBP. CBP itself is a phosphoprotein and can be phosphorylated by cycle-dependent kinases or by MAP kinases. Here we show that CBP phosphorylation by p44 MAP kinase/ERK1 results in the stimulation of its HAT enzymatic activity. The p44 MAP kinase/ERK1 phosphorylation sites are located in the C-terminal part of the protein, outside of the HAT domain. These sites are required for enzymatic stimulation, suggesting that phosphorylation by p44 MAP kinase/ERK1 induces a conformational change of the CBP molecule. Our data suggest that, in some instances, CBP itself might be a target for signal transduction pathways.
Ait-Si-Ali
S
S
Différenciation et Transduction du Signal, CNRS UPR 9079, IFC-01, Villejuif, 94801, France.
Carlisi
D
D
Ramirez
S
S
Upegui-Gonzalez
L C
LC
Duquet
A
A
Robin
P
P
Rudkin
B
B
Harel-Bellan
A
A
Trouche
D
D
D016475:3T3 Cells; D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050882:CREB-Binding Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000255:Adenosine Triphosphate; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D051548:Histone Acetyltransferases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases