c-Fos physically associates with and activates specific enzymes of the pathway of phospholipid synthesis

CAPUTTO BL

Potrero de los Funes, San Luis

Simposio; Simposio de Lípidos de la XLVII Reunión Annual de SAIB; 2011

SAIB

c-Fos physically associates and activates specific enzymes of the pathway of phospholipid synthesis Caputto, BL, Cardozo Gizzi A, Ferrero GO, Velázquez FN. CIQUIBIC – Depart. Química Biológica, Facultad de Ciencias Químicas, Univ. Nac. Córdoba, Argentina. We previously showed that c-Fos has, in addition to its well known AP-1 transcription factor activity, the capacity to associating to the endoplasmic reticulum (ER) and activating key enzymes of phospholipid and glycolipid synthesis in events related to normal growth or the exacerbated growth characteristic of tumor cells. c-Fos/ER-association and consequently its lipid activation capacity is regulated by the phosphorylation state of c-Fos tyrosine residues. Herein we show that c-Fos physically associates to the enzymes that it activates; no interaction is observed between c-Fos and enzymes it does not activate. c-Fos activates and immunoprecipitates CDP-DAG synthase (CDS) and PtdIn 4K (PI4K) but not PtdIn Synthase (PIS). Direct physical association was confirmed by FRET (Fluorescence Resonance Energy Transfer) assays.Positive FRET was observed between c-Fos and CDS and c-Fos with PI4K but not with PIS. The N-terminal of c-Fos is required for its association to these enzymes whereas its basic domain (amino acids 139-159) is responsible for enzyme activation. c-Fos expression is tightly regulated by specific environmental cues, assuring that lipid metabolism activation will occur as a response to cell requirements. Thus, c-Fos emerges as an important regulator of key membrane metabolisms in membrane-biogenesis demanding processes such as normal and exacerbated growth.