[Abnormal p53-HDM2 interaction in hematological malignancy]

The tumor suppressor protein p53 is a multifunctional transcription factor involved in the control of cell survival and death. p53 is inactivated by mutation of the p53 gene in approximately 50% of human cancers. While the rest (including hematological malignancies) encode wild-type p53, p53 is frequently inhibited by its negative regulator human double minute 2 (HDM2). HDM2 is a p53-specific E3 ubiquitin ligase. Therefore, there has been considerable interest in identifying compounds for disrupting the p53-HDM2 interaction. Small-molecule antagonist of HDM2, which binds HDM2 in the p53-binding pocket, negatively controls the activity of HDM2 and prevents p53 degradation. This stabilization of p53 results in its activation, leading to cell cycle arrest, growth inhibition, and apoptosis in wild type p53-haboring hematological malignant cells. Biology of p53-HDM2 interaction and anti-tumor effects of the HDM2 inhibitor in hematological malignant cells are described in this review.