Although induction of apoptosis was observed in both HepG2 (wild type) and HLE (R249S) cells, restoration of p53 transcriptional activity was only detected in XI-011-treated HepG2 cells, suggesting that MDM4 has a yet unknown p53-independent tumor suppressive function, which was also detectable in p53-depleted Hep3B cells. This evidence concerns the gene MDM4 and neoplasm.