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

与 B-Myb 的直接结合强加细胞质磷脂酶 A2 的核来调节 B-Myb 依赖的 go 表达

• 批准号: 11671871
• 负责人: TASHIRO Sigeki
• 金额: $ 1.98万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671871/
• 关键词: cPLA2; CaLB domain; nuclear export signal; intramolecular interaction; localization; transcriptional factor

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.

胞浆磷脂酶A2（cPLA 2）裂解膜磷脂以释放花生四烯酸，启动脂氧合酶和环氧合酶途径。缺乏cPLA 2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。cPLA 2被细胞因子、亚微摩尔浓度的Ca 2+离子和MAP激酶介导的蛋白质中丝氨酸残基的磷酸化激活3.4。活化的cPLA 2蛋白优先分布于细胞的核周区域4 -7，在那里酶被认为参与花生四烯酸的释放。在这里，我们表明，cPLA 2直接和特异性结合的B-Myb转录因子，因此，cPLA 2易位到细胞核。结合位点分析表明cPLA 2的N-和C-末端均与B-Myb的C-末端相互作用。结果还表明，cPLA 2-B-Myb复合物的形成和易位到细胞核与B-Myb依赖性基因表达的调节有关。这些发现为cPLA 2对B-Myb功能的核内调节提供了新的见解。