N-terminal c-Fos dephosphorylation is required for c-Fos dependent phospholipids synthesis activation

MAXIMILIANO MOISES PORTAL; GABRIEL ORLANDO FERRERO; BEATRIZ LEONOR CAPUTTO

Iguazu

Simposio; Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2004

Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

c-Fos is a component of AP-1 transcription factor family that regulates genes involved in proliferation and differentiation. c- Fos is not a constituent component of cells but its expression is rapidly and transiently induced by trophic factors. We disclosed an additional activity of c-Fos, that is its capacity to associate to the ER and activate phospholipid synthesis. Herein we report, the molecular constraints that determine c-Fos/ER association and consequently its phospholipid synthesis activation capacity. In quiescent cells, the small amounts of c-Fos present are phosphorylated in Tyr residues, a novel phosphorylation site for c-Fos. Induction of cells to re-enter the cell cycle results in the loss of Tyr phosphoryl groups present in preformed c-Fos, and additional c-Fos expression. Dephosphorylated c-Fos now associates to the ER and activates phospholipid synthesis. If dephosphorylation is impaired, phospholipid synthesis activation is not observed and proliferation rates diminish. Recombinant c- Fos associates to ER and activates phospholipid synthesis whereas purified Tyr-phosphorylated c-Fos does not. Using c-Fos deletion mutants, it was found phosphorylation/ dephosphorylation in all C-terminal deletion mutants. Previous studies have shown Ser/ Thr phosphorylation as a delicate mechanism to regulate c-Fos transactivation capacity. Herein we postulate that c-Fos Tyrphosphorylation is a regulatory event that determines the rate of phospholipid synthesis by regulating c-Fos/ER association, thus being a key event in cell cycle progression.