p53 family network and human cancer

Since the 1980s cancer is the leading cause of death in Japan. Most human cancers exhibit inactivation of the p53 network, either through direct mutation of p53,or through disruption of regulatory pathways essential for p53 function.The tumor suppressor gene p53 encodes a transcriptional activator as a nodal point for cellular responses to several stress conditions. p53 is one of the most highly connected nodes in the cell,and an attack on p53 by mutation will disrupt basic cellular functions, particularly responses to DNA damage and tumor-predisposing stresses. p63 and p73 are functionally and structurally related to the tumor suppressor p53. Recent findings from others and us have provided evidence for a broader role for the p53 family than were previously reported. In this review, we provide an overview of the networks controlled by the p53 family as a framework for developing p53 family-based strategies to treat cancer.departmental bulletin pape