Ait-Si-Ali S, Carlisi D, Ramirez S, Upegui-Gonzalez L C, Duquet A, Robin P, Rudkin B, Harel-Bellan A, Trouche D
Différenciation et Transduction du Signal, CNRS UPR 9079, IFC-01, Villejuif, 94801, France.
Biochem Biophys Res Commun. 1999 Aug 19;262(1):157-62. doi: 10.1006/bbrc.1999.1132.
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.
转录共激活因子CBP具有内在的组蛋白乙酰转移酶（HAT）活性，该活性似乎通过破坏核小体结构参与转录激活。CBP参与多种转录因子的活性，这些转录因子是细胞内信号转导途径的核内终点。在某些情况下，转录因子在细胞激活时被磷酸化，从而诱导它们与CBP相互作用。CBP本身是一种磷蛋白，可被周期依赖性激酶或丝裂原活化蛋白激酶磷酸化。在此我们表明，p44丝裂原活化蛋白激酶/ERK1对CBP的磷酸化导致其HAT酶活性增强。p44丝裂原活化蛋白激酶/ERK1的磷酸化位点位于该蛋白的C末端部分，在HAT结构域之外。这些位点是酶活性增强所必需的，表明p44丝裂原活化蛋白激酶/ERK1的磷酸化诱导了CBP分子的构象变化。我们的数据表明，在某些情况下，CBP自身可能是信号转导途径的一个靶点。
