Phosphorylation by p44 MAP kinase/ERK1 stimulates CBP histone acetyl transferase activity in vitro
Phosphorylation by p44 MAP kinase/ERK1 stimulates CBP histone acetyl transferase activity in vitro
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DOI：
10.1006/bbrc.1999.1132
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发表时间：
1999-08-19
影响因子：
3.1
通讯作者：
Trouche, D
中科院分区：
文献类型：
--
作者：
Ait-Si-Ali, S;Carlisi, D;Trouche, D
转录共激活子CBP显示出内在的组蛋白乙酰转移酶(HAT)活性，它似乎通过核小体结构的失稳参与转录激活。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通路的核端点。在某些情况下，转录因子在细胞激活时被磷酸化，这导致它们与CBP相互作用。CBP本身是一种磷酸化蛋白，可以被周期依赖的激酶或MAP激酶磷酸化，在这里，我们证明了P44 MAP激酶/ERK1对CBP的磷酸化导致其HAT酶活性的刺激。P44MAPK/ERK1磷酸化位点位于蛋白质的C末端，在HAT结构域之外。这些位点是酶刺激所必需的，这表明p44 MAP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本身可能是信号转导途径的目标，(C)1999年学术出版社。
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, (C) 1999 Academic Press.