Our results also suggest that HDAC inhibition induces ITCH activation and formation of ITCH-UBE4B ubiquitin ligase complex that recruits Ku70 and c-FLIPL for polyubiquitination and degradation, leading to induction of apoptosis and suggesting that the association of UBE4B expression with neuroblastoma patient outcomes may be mediated by effects on responses of patient tumors to therapy via the ITCH-UBE4B complex. This evidence concerns the gene ITCH and neuroblastoma.