Skip to main content
. 2016 Feb 1;2:16003. doi: 10.1038/cddiscovery.2016.3

Figure 2.

Figure 2

Downregulation of selected IRES targets is regulated by caspase-3 except for c-Myc, which is regulated by K-Ras inhibition. (ac) Caspase-3 inhibition restores the expression of selected IRES targets but fails to protect c-Myc and N-Myc. Caspase-3 inhibitor z-DEVD-fmk restored Myc isoforms in TNF-α+AZ58-treated cells at (a) 8 h but failed to restore c-Myc and N-Myc at (b) 24 h. Bar graphs in panel (a) indicate that the DNA fragmentation was prevented by z-DEVD-fmk in all conditions (n=3). The simplified schematic diagram in panel (c) explains the action of z-DEVD-fmk on p70S6K and IRES targets. (d) Caspase-3 inhibition prevents secondary necrosis in blebbishields generated by TNF-α+AZ58 (arrows, secondary necrosis). (e) MW shift (oligomers) of K-Ras with FasL+AZ58 differs in quantity from MW shift with TNF-α+AZ58 or TRAIL+AZ58. (f) K-Ras activation assay. GST-Raf1-RBD binding to K-Ras was abolished by AZ58 combinations with TNF-α, FasL, and TRAIL.