Figure 5. Proposed working model by which K8/K18 regulates apoptosis via DR5.

K8/K18 proteins are found to be upregulated in TRAIL-resistant cancer cells. K8/K18 pair appears to physically interacts with DR5, restricting the receptor inside the cells (e.g., localized in nuclear and perinuclear compartments) (Route I). Loss of K8/K18 results in translocation of DR5 to the cell surface, thereby restoring apoptotic signaling via DR5 (Route II). Other cytoskeleton components (e.g., tubulin and actin) and interacting proteins (e.g., catenin and E-cadherin) may be integral in the regulation of death receptor mediated apoptosis.