Fig. 10. The effect of eIF3k on the cleavage of caspase 3 nuclear and cytosolic substrates. (A) Downregulation of eIF3k diminishes the cleavage of ICAD and PARP. SW13 or SW13-K8/K18 cells expressing eIF3k siRNA or control siRNA were irradiated with UV at 0.015 J/cm2 and then cultivated for 6 hours (for SW13 cells) or 7 hours (for SW13-K8/K18 cells). Cells were then lysed for western blot analyses with antibodies as indicated. The positions of full-length (116 kDa) and truncated (85 kDa) PARP are indicated. The bands shown in the ICAD blot represent full-length ICAD. (B) Model of eIF3k function during apoptosis. eIF3k is associated with K8/K18 filaments in non-apoptotic cells. Upon induction of apoptosis, procaspase 3 is concentrated in the K8/K18 network (Lee et al., 2002). This leads to a local activation of caspase 3, which in turn cleaves K18. After disintegration of the keratin filaments, cytoplasmic inclusion bodies are formed, which sequester K8, K18, eIF3k and several apoptotic-promoting factors (omitted). In this study, we show that eIF3k inhibits the association of active caspase 3 with K18 and therefore releases this caspase to the cytosol.