METHOD OF MODULATING PROAPOPTOTIC AND ANTIAPOPTOTIC PATHWAYS IN CELLS

摘要

More than 30 % of human malignancies harbor encogenic Ras. Both pro-apoptotic and anti-apoptotic pathways emanate from encogenic Ras with survival being dominant. Ras survival signaling is thought to be controlled by transcriptional and post-translational processes. The present invention shows that a repressor of cap-dependent translation initiation, 4E-BP1, selectively activates apoptosis in Ras-transformed fibroblasts and eliminates Ras-induced chemoresistance. These effects of 4E-BP1 are strictly dependent on its ability to sequester translation initiation factor elF4E, thereby preventing its assembly into an active pre-initiation complex. These results suggest that translational control is critical for prevention of apoptosis and resistance to antitumor agents in Ras-transformed cells.