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

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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.