c-Fos Activates and Physically Interacts with Specific Enzymes of the Pathway of Synthesis of Polyphosphoinositides

NDRES M. CARDOZO GIZZI, ADOLFO R. ALFONSO PECCHIO, BEATRIZ L. CAPUTTO

Buenos Aires

Simposio; Frontiers in BioScience; 2012

Max Planck Society y el Ministerio de Ciencia, Tecnologia e Innovacion Productiva de la Nacion

The oncoprotein c-Fos is a well-recognized AP-1 transcription factor. In addition, this protein associates with the endoplasmic reticulum and activates the synthesis of phospholipids. However, the mechanism by which c-Fos stimulates the specific lipid pathways is unknown. We investigated whether stimula¬tion by c-Fos of the synthesis of phosphatidylinositol and its phosphorylated derivatives depends on the activation of enzymes of the phosphatidylinositolphosphate biosynthetic pathway. We found that c-Fos activates CDP-diacylglycerol synthase and phosphatidylinositol (PtdIns) 4-kinase II α in vitro, whereas no activation of phosphatidylinositol synthase or of PtdIns 4-kinase II β was observed. Both coimmunoprecipitation and fluorescence resonance energy transfer experiments consistently showed a physical interaction between of c-Fos and the enzymes it activates.