Germ-Line-derived Hinge Domain p53 Mutants Have Lost Apoptotic but not Cell Cycle Arrest Functions¹

The protein p53 is a critical tumor suppressor, as demonstrated by its frequent mutation in human cancers. Overexpression of the wild-type form of the p53 tumor suppressor gene in human cancer cell lines has been shown to lead to either cell cycle arrest or apoptosis. A study of two Li-Fraumeni syndrome-derived p53 hinge domain mutants shows that both mutants retain the ability to arrest cell growth but are significantly impaired for the induction of apoptosis in human p53-null cell lines. This indicates that the hinge domain may be important in the regulation of p53-dependent apoptosis.