Participation of c-Fos in activating protein synthesis in differentiating PC12 cells

DURAND E.S.; CAPUTTO B.L.

Mar del Plata

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

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

We have found that c-Fos, in addition to being a member of the AP-1 family of transcription factors, associates to the endoplasmic reticulum (ER) and activates the synthesis of phospholipids in events that require membrane biogenesis. The complex process of membrane biogenesis requires not only lipids but also other components such as proteins. It was examined if c-Fos also activates protein synthesis by an AP-1 independent mechanism. PC12 cells in culture induced to differentiate by feeding with nerve growth factor (NGF) and labeled with 35S-methionine showed that blocking c-Fos expression inhibits NGF-activated protein synthesis; culturing cells with a peptide that specifically blocks the nuclear import of AP-1-c-Fos shows that AP-1 is required to trigger protein synthesis whereas cytoplasmic c-Fos is necessary for this process to continue. To establish if the activation of protein synthesis by c-Fos is a direct effect on the ER we performed in vitro translation. Increasing concentrations of recombinant c-Fos were incubated with the rabbit reticulocyte system in the presence of canine pancreatic microsomal membranes and a signal sequence mRNA. Preliminary results show activated protein biosynthesis that was dependent on the concentration of recombinant c-Fos. It is hypothesized that c-Fos, in addition to activating lipid synthesis in the ER, activates that of proteins.