Cytoplasmic c-Fos activates the translation in differentiating PC12 cells and in vitro systems

DURAND E.S.; CAPUTTO B.L

Carlos Paz

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

We have found that c-Fos, in addition to its activity as a member of the AP-1 family of transcription factors, associates to the ER and activates the synthesis of phospholipids in events that require membrane biogenesis. However, membrane biogenesis not only requires lipids, it also requires other components such as proteins. Consequently, we examined if c-Fos also activates protein synthesis by an AP-1 independent mechanism. Cultured PC12 cells induced to differentiate by feeding with NGF showed an increased in protein synthesis; this activation was abolished upon blocking of c-Fos expression; culturing cells with a peptide that specifically blocks the nuclear import of AP-1-c-Fos or with a specific inhibitor of p38 MAPKs that phosphorylate c-Fos transactivation domain shows that AP-1 is required to trigger neuronal differentiation whereas cytoplasmic c-Fos is necessary for differentiation to continue. Neuronal differentiation positively correlates with protein synthesis activation. In vitro translation shows activated protein biosynthesis in the ER that is dependent on the concentration of c-Fos and on the c-Fos/ER association. Similar results were found with a synthetic peptide containing the 22 basic aa of the BD of c-Fos. This is the first evidence that c-Fos can activate, in addition to the metabolism of lipids, protein metabolism.