Wild Type p53 conformation, structural consequences of p53 mutations and mechanisms of mutant p53 rescue

Andreas C. Joerger*, Assaf Friedler, Alan R. Fersht

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

6 Scopus citations

Abstract

The tumor suppressor p53 is a transcription factor that is at the center of a network of interactions that affect the cell cycle and apoptosis (Vogelstein et al. 2000; Ryan et al. 2001). The protein is induced by a variety of stresses that include oncogene activation and DNA damage caused by chemotherapy and radiotherapy. On induction, it activates a variety of genes whose products lead to G1 and G2 cell cycle arrest and apoptosis (Vogelstein et al. 2000; Ryan et al. 2001). It is such an effective tumor suppressor that it is inactivated in virtually all cancers; in about 50 % of cancers p53 is directly inactivated by mutation and in the remainder its activity is lost by perturbations of its associated pathways and interactions (Hainaut and Hollstein 2000). Reactivating mutant p53 is an important target in the development of novel therapies for cancer (Lane and Lain 2002; Lane and Hupp 2003). To understand how p53 is inactivated, it is necessary to understand its structure and how it responds to mutation. Such knowledge will provide a basis for the rational design of novel therapeutics that may reverse the effects of mutation. In this chapter, we survey the structure of the protein, the effects of mutation and how they may be reversed.

Original languageAmerican English
Title of host publication25 Years of p53 Research
PublisherSpringer Netherlands
Pages377-397
Number of pages21
ISBN (Electronic)9781402029226
ISBN (Print)9781402029202
DOIs
StatePublished - 2005
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2007 Springer. All Rights Reserved.

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