RESUMEN
c-Fos is a well-recognized member of the AP-1 (activator protein-1) family of transcription factors. In addition to this canonical activity, we previously showed that cytoplasmic c-Fos activates phospholipid synthesis through a mechanism independent of its genomic AP-1 activity. c-Fos associates with particular enzymes of the lipid synthesis pathway at the endoplasmic reticulum and increases the Vmax of the reactions without modifying the Km values. This lipid synthesis activation is associated with events of differentiation and proliferation that require high rates of membrane biogenesis. Since lipid synthesis also occurs in the nucleus, and different phospholipids have been assigned transcription regulatory functions, in the present study we examine if c-Fos also acts as a regulator of phospholipid synthesis in the nucleus. Furthermore, we examine if c-Fos modulates transcription through its phospholipid synthesis activator capacity. We show that nuclear-localized c-Fos associates with and activates PI4P5K (phosphatidylinositol-4-monophosphate 5-kinase), but not with PI4KIIIß (type IIIß phosphatidylinositol 4-kinase) thus promoting PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) formation, which, in turn, promotes transcriptional changes. We propose c-Fos as a key regulator of nuclear PtdIns(4,5)P2 synthesis in response to growth signals that results in c-Fos-dependent transcriptional changes promoted by the newly synthesized lipids.
Asunto(s)
Núcleo Celular/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Transcripción Genética , Regulación hacia Arriba , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Núcleo Celular/efectos de los fármacos , Núcleo Celular/enzimología , Núcleo Celular/ultraestructura , Tamaño del Núcleo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Ratones , Células 3T3 NIH , Proteínas Asociadas a Matriz Nuclear/genética , Proteínas Asociadas a Matriz Nuclear/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , Interferencia de ARN , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Transcripción Genética/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The stability and reusability of a promising bimetallic mesoporous catalyst (5Na/20Ce/SBA-15) to produce first- and second-generation biodiesel was studied. Soybean oil, waste frying oil, and Jatropha hieronymi oil were used as lipid raw materials. Under optimized reaction conditions (10â wt % of catalyst, methanol to oil molar ratio of 40 : 1, 60 °C, and vigorous magnetic stirring), the minimum FAME content required by the ENâ 14214 standard was achieved in 3â h with soybean oil and waste frying oil. Three alternatives were considered concerning the reuse of the catalyst (without and with regeneration), concluding that washing followed by calcination between each run is suitable for the material to recover its activity. FAME contents over 87â wt % were obtained in five cycles when using waste frying oil. Key quality properties of the produced biofuel were evaluated and found to comply with international standards for its commercialization as automotive diesel fuel without further treatment.