c-Fos PHYSICALLY INTERACTS AND ACTIVATES SPECIFIC POLIPHOSPHOINOSITIDE SYNTHESIS ENZYMES

CARDOZO GIZZI AM, ALFONSO PECCHIO A, CAPUTTO BL

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

The oncoprotein c-Fos, in addition to its well described function as a transcription factor belonging to AP-1 family, associates with the endoplasmic reticulum (ER) and activates key enzymes involved in the synthesis of phospholipids. To attain an overall activation of phospholipid synthesis, only particular enzymatic activities were positively affected. Herein, it was examined which enzymes of the PtdInsP biosynthetic pathway are activated by c-Fos, In order to understand the mechanism of enzyme activation, analysis of protein-protein interactions between c-Fos and different phospholipid enzymes by co-immunoprecipitation and Fluorescence Resonance Energy Transfer (FRET) were performed. It was found that c-Fos specifically associates to and activates the enzymes CDP-diacylglycerol synthase (CDS) and PtdIns4 Kinase II alpha (PI4KIIa), whereas neither association nor activation of Phosphatidylinositol Synthase (PIS) or PtdIns4 Kinase II beta (PI4KIIß) were observed. Finally, it was observed that depending on the cellular content of c-Fos, the channelling of the common precursor PtdOH could be directed towards the Kennedy or to the PtdIns pathway of phospholipid synthesis, suggesting a new mode to balance between these pathways as a function of the immediate requirements of cells.