title: c-Fos activates and physically interacts with specific enzymes of the pathway of synthesis of polyphosphoinositides.
abstract: 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 synthesis of phospholipids in general and the specific lipid pathways activated are unknown. Here we show that induction of quiescent cells to reenter growth promotes an increase in the labeling of polyphosphoinositides that depends on the expression of c-Fos. We also investigated whether stimulation 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 the N-terminal domain of c-Fos and the enzymes it activates.
authors: Centro de Investigaciones en Química Biológica de Córdoba (Consejo Nacional de Investigaciones Científicas y Técnicas), Departamento de Química Biológica, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
authors: Adolfo R
authors: AR
authors: Alfonso Pecchio
authors: Andrés M
authors: AM
authors: Cardozo Gizzi
authors: Marianne L
authors: ML
authors: Renner
authors: María
authors: M
authors: Molina-Calavita
authors: Beatriz L
authors: BL
authors: Caputto
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002798:Diacylglycerol Cholinephosphotransferase / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation / Q000502:physiology; D004790:Enzyme Induction / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis* / Q000235:genetics; D010743:Phospholipids / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018129:Phosphatidylinositol Phosphates; D010743:Phospholipids; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D019870:1-Phosphatidylinositol 4-Kinase; D002798:Diacylglycerol Cholinephosphotransferase