Chapter category: Oncogenes
Lessons on p53 from Mouse Models
p53
Edited by: Theodore Hupp and Ayeda AyedISBN: TBA141
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Chapter authors:
Laura D. Attardi*
Mutations in the p53 gene are implicated in the development of at least half of all human cancers, of a wide variety of types.1,2 This high incidence of mutations suggests that there exists a strong selection pressure for p53 inactivation during tumorigenesis. The idea that p53 mutations are important for tumor development in humans has also been supported by the finding that in the Li-Fraumeni syndrome, individuals inherit a mutant p53 allele and show a predisposition to developing a wide variety of cancers.3 An unambiguous cause and effect relationship, however, between p53 mutation and tumorigenesis has been clearly provided through the generation and analysis of p53 knockout mice.4-6 p53 null mice are subject to tumorigenesis at 100% frequency, indicating that the presence of p53 is crucial for preventing cancer development. In addition to this initial observation, significant understanding of the role of p53 as a tumor suppressor has come through further analysis of the p53 knockout mouse as well as other versions of mice with altered p53 genes. In this chapter, I will summarize the p53 knockout mouse, p53 knock-in models, as well as p53 transgenics, and how these models have helped us to understand p53 function in vivo.
Additional chapters from this book:
Lessons on p53 from Mouse Models
Laura D. Attardi*
Mutations in the p53 gene are implicated in the development of at least half of all human cancers, of a wide variety of types.1,2 This high incidence of mutations suggests that there exists a strong...
TP63, TP73: The Guardian’s Elder Brothers
Stephanie Courtois, Pierre Hainaut and Claude Caron de Fromentel
TP73 and TP63 recently emerged as sharing overall architectural similarities with TP53. Phylogeny indicates that these three genes derive from a common ancestor, thus defining a new gene family. All...
Modes of p53 Interactions with DNA in the Chromatin Context
Vladana Vukojevic, Tatiana Yakovleva and Georgy Bakalkin
The tumor suppressor p53, a sequence-specific transcription factor playing a central role in cancer surveillance, exerts its main functions by activating or repressing transcrip tion of its target g...
TP53 Mutations in Human Cancers: Selection versus Mutagenesis and Pierre Hainaut
Magali Olivier, Stephanie Courtois, Claude Caron de Fromentel and Pierre Hainaut
TP53 differs from most other cancer-related genes by the very high prevalence of missense mutations which result in the expression of a mutant protein. Considerable variations are observed between m...
Tumor Viruses and p53
Nobuo Horikoshi
Viruses are potent oncogenic agents and are considered to link to approximately one-fifth of all human malignancies. The study of tumor viruses has provided fundamental bases of how normal cells bec...
The p53-Mdm2 Loop A Critical Juncture of Stress Response
Zehavit Goldberg, Igal Louria-Hayon, Tamar Grossman, Michael Berger and Ygal Haupt
The presence of a functional p53 protein is a key factor for the proper suppression of cancer development. A loss of p53 activity, by mutations or inhibition, is often associ ated with human maligna...
Regulation of p53 Localization
Tomomi Inoue, Carl G. Maki
The tumor suppressor protein p53 is one of the most intensely studied molecules in modern cancer biology, and with good reason. Inactivating mutations in the p53 gene are observed in over 50% of all...
p53’s Dilemma in Transcription: Analysis by Microarrays
Karuppiah Kannan, Gideon Rechavi and David Givol
Protection against cancer by p53 is due mainly to its activity as a transcription factor. The function of p53 in transactivation of target genes is analyzed here with emphasis on the dilemma between...
