Aspectos mecanísticos de c-Fos en la regulación de la síntesis de fosfolípidos

GABRIEL ORLANDO FERRERO; BEATRIZ LEONOR CAPUTTO

Puerto Madryn

Simposio; Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2010

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

The expression of the proto-oncoprotein c-Fos is tightly regulated responding rapidly and transiently to a plethora of stimuli. c-Fos heterodimerizes with jun proteins to form AP-1 transcription factors that regulate the expression of target genes such as those involved in DNA synthesis. Although described more than 20 years ago, a precise molecular understanding of the participation of AP-1 in complex processes such as proliferation and growth has not yet been achieved. In our laboratory, we have identified an additional activity of c-Fos independent of its AP-1 activity. This is its capacity to associate to the endoplasmic reticulum (ER) and activate lipid synthesis. In T98G cells, the association of c-Fos to the ER and, consequently, the capacity of c-Fos to activate phospholipid synthesis is regulated by the phosphorylation state of its tyrosine residues #10 and #30. The small amount of c-Fos present in quiescent cells is tyrphosphorylated, dissociated from the ER membranes and does not activate phospholipid synthesis. However, upon induction of cells to re-enter growth, c-Fos is rapidly induced, found dephosphorylated, associated to ER membranes and activates phospholipid synthesis. Herein, using in vivo and in vitro experimental strategies, it was found that c-Src is capable of phosphorylating c-Fos tyr residues whereas the phosphatase TC45 (TC-PTP) dephosphorylates them.