Proteasomal insensitivity of apoptin in tumor cells

The small viral protein apoptin is capable of inducing apoptosis selectively in human tumor cells. In normal cells apoptin localizes in the cytoplasm where it forms aggregates, becomes epitope-shielded and eventually degraded. By inhibiting the proteasome activity with the chemical inhibitors bortezomib and Ada-Ahx3L3VS apoptin levels can be stabilized in normal cells similar to the tumor suppressor p53 protein. In contrast, proteasome inhibition in tumor cells did not affect the apoptin stability while it still stabilized p53 levels. Apparently, apoptin is degraded by proteasomal activity in normal human cells, a process that no longer takes place in tumor cells. This loss of proteasomal susceptibility appears to be specific for apoptin.

► Apoptin induces apoptosis in tumor cells and leaves normal cells unharmed.
► Proteasomal degradation of apoptin differs between normal/tumor cells (unlike p53).
► This differential trait underpins apoptin as a safe anti-cancer agent.