Mechanisms of regulation of phospholipids synthesis by c-Fos and Fra-1. Implications in proliferation of brain tumors

CÉSAR G. PRUCCA; BEATRIZ L. CAPUTTO

Sorrento, Naples

Otro; Advanced Course: Lipid Signaling and Cancer. FEBS; 2012

FEBS

c- Fos as well as Fra-1 belongs to the AP-1 family of transcriptions factors. After 20 years of research it?s not completely unrevealed the function of these factors associated with the progression of several types of tumors. During the last years, our laboratory has studied the association of the activity of these transcription factors; principally c-Fos; with the biosynthesis of phospholipids, the principal components of cell membranes. c-Fos has shown to be able to associate to the endoplasmic reticulum (ER) and activate the biosynthesis of phospholipids and glycolipids. This association has been confirmed by co-inmunoprecipitation and FRET (Flourescence Resonance Energy Transfer). Studies using deletion mutants of c-Fos permit us to recognize the unique domain of c-Fos that is able to associate to the ER but does not activate phospholipids synthesis. Currently, we are carrying out studies using these mutants with the final aim of diminishing/blocking phospholipids synthesis, and in consequence abolishing cell division. A preliminary result indicates that if we disrupt the activation of phospholipids synthesis by means of expression of a negative dominant there is a reduction in the cell division. On another hand, in a model of breast tumor, we observed that Fra-1 is highly expressed compared with normal tissues. Moreover, like c-Fos, this protein associates to the ER and has an AP-1 independent activity that promotes phospholipids synthesis activation. Based in these results, we continued the studies in our brain tumor model adding now Fra-1 as a putative target for blocking cell proliferation and in consequence, tumor progression.