Does control of mutant p53 by Mdm2 complicate cancer therapy?

Abstract

Missense mutant forms of p53 are expressed at high levels in some human cancers and may contribute to oncogenesis. In this issue of Genes & Development, Terzian and colleagues (pp. 1337–1344) describe a mutant p53 knock-in mouse in which normal tissues and some tumors have low levels of mutant p53 protein unless Mdm2 or p16^INK4A are absent. Once stabilized, mutant p53 promotes metastasis. Therefore, therapies that release p53 from Mdm2 might have unwanted consequences when cells have sustained a mutation in p53.

Keywords

• Metastasis
• mouse model
• gain of function
• p53 stability