Direct binding with B-Myb imposes nuclear of cytoplasmic phosphlipase A2 to regulate B-Myb-dependent gone expression

胞质磷脂酶A2 （cPLA2）裂解膜磷脂释放花生四烯酸，启动脂氧合酶和环氧合酶途径。缺乏cPLA2基因的小鼠表现出过敏反应和生育能力受损，并且可能在神经元细胞死亡方面存在缺陷1,2。cPLA2被细胞因子、亚微摩尔浓度的Ca2+离子和MAP激酶介导的蛋白中丝氨酸残基磷酸化激活。活化的cPLA2蛋白优先分布于细胞的核周区域4-7，该酶被认为参与花生四烯酸的释放。在这里，我们发现cPLA2直接和特异性地结合到B-Myb转录因子上，因此，cPLA2易位到细胞核中。结合位点分析表明，cPLA2的n端和c端都与B-Myb的c端相互作用。结果还表明，cPLA2-B-Myb复合物的形成和向细胞核的易位与b- myb依赖性基因表达的调控有关。这些发现为cPLA2对B-Myb功能的核内调控提供了新的见解。

Cytosolic phospholipase A2 (cPLA2) cleaves membrane phospholipids to release arachidonic acid, initiating lipoxygenase and cyclooxygenase pathways. Mice lacking a gene for cPLA2 exhibit impaired allergic responses and fertility, and may have defects in neuronal cell death1,2. cPLA2 is activated by cytokines, submicromolar concentrations of Ca2+ ions, and MAP kinase-mediated phosphorylation of serine residues in the protein3.4. Activated cPLA2 protein distributes preferentially to the perinuclear region of the cell4-7, where the enzyme is thought to participate in arachidonic acid release. Here we show that cPLA2 binds directly and specifically to the B-Myb transcription factor and that, as a result, cPLA2 translocates into the nucleus. Binding site analysis demonstrated that both the N-and C-termini of cPLA2 interact with the C-terminus of B-Myb. The results also demonstrate that formation of cPLA2-B-Myb complexes and translocation to the nucleus is associated with regulation of B-Myb-dependent gene expression. These findings provide new insights into the intranuclear regulation of B-Myb function by cPLA2.