ACTIVATION OF LIPIN BY C-FOS: UNDERSTANDING THE INTERACTION THROUGH LIPIN

SUAREZ, T.; CAPUTTO BL; PRUCCA CG

Parana

Congreso; 54 Reunion Anual de la Sociedad Argentina de Bioquímica y Biología Molecular; 2018

Sociedad Argentina de Bioquímica y Biología Molecular

c-Fos is a proto-oncoprotein that associates with components of the endoplasmic reticulum (ER) and activates the synthesis of phospholipids andglycolipids by a mechanism independent of it´s genomic activity. c-Fos activates different enzymes involved in the synthesis of phospholipidsand glycolipids that do not share similar structures or homology in their sequence, among them the enzyme phosphatidic acid phosphatase(Lipin). Lipin uses Phosphatidic acid (PA) as substrate and produces Diacylglycerol that will be used in the synthesis of phospholipids orphosphatidylinositides. Enzymes of the Lipin family are present in most tissues and are distributed both at the nucleus and in the cytoplasm; theyare not integral membrane proteins but translocate from the cytoplasm to ER membranes to participate in the synthesis processes. It has beenshown that Lipin interacts with the N-terminal domain of c-Fos and is activated through the basic domain of this protein (BD). The aim of ourwork is to study the Lipin domains involved in the interaction with c-Fos in order to understand the biology of the interaction between theseenzymes and c-Fos. To this end, four enzyme deletion mutants fused to GFP were generated and its subcellular localization was observed inT98G cells (human glioblastoma multiforme), the subcellular localization and Lipin expression levels in synchronized cultures were alsoanalyzed, comparing their expression to that observed for c-Fos. We are currently studying the interaction between these deletion mutants and c-Fos by FRET microscopy.