25 Years of p53 Research

p53 has emerged as a key tumor suppressor and important target for novel cancer therapy. This book, written by world-leading p53 researchers including many of those who have shaped the field over the past 25 years, provides unique insights into the progress of the field and the prospects for better cancer diagnosis and therapy in the future.

Zusammenfassung

1. Communication, awareness and access to information: Given the complexity of the field and the fact that data pertaining to each particular aspects of p53 biology or deregulation are scattered in many different publications, it is extremely difficult to access the full scale of relevant information of any specific p53-related topic. Review arcticles, despite their fundamental role in disseminating knowledge, usually focus only on general mechanisms and do not discuss in detail the many variations that can occur with respect to cell type, particular mutation type, as well as biological activation context. Books such as this one may help in this task by putting into perspective both general considerations on the p53 pathway and more specific information on various aspects of p53. In the longer term, however, open access to p53 complexity will require the development of knowledge bases accessible through the web and using simple navigation tools to guide users towards the specific information they need. Several efforts are currently being developed in that direction. They need to be strenghtened and better integrated within the rapidly growing galaxy of web-based information sources on molecular and individual variations in cancer. 2. Reference functional assays and structural analysis: Given the huge diversity of cellular and animal models for wild-type or mutant p53 functions, it will be important to set up standard, universally accepted assays to measure critical p53 protein functions.

Inhalt

The First Twenty-Five Years of p53 Research.- Regulation of p53 DNA Binding.- 20 Years of DNA Damage Signaling to p53.- Gatekeepers of the Guardian: p53 Regulation by Post-Translational Modification, MDM2 and MDMX.- Regulation of the p53 Response by Cellular Growth and Survival Factors.- P53, Cell Cycle Arrest and Apoptosis.- P53 Has a Direct Pro-apoptotic Action at the Mitochondria.- Manipulating the p53 Gene in the Mouse: Organismal Functions of a Prototype Tumor Suppressor.- P53, P63, and P73: Internecine Relations?.- P73, P63 and Mutant P53: Members of Protein Complexs Floating in Cancer Cells.- P53: Gatekeeper, Caretaker or Both?.- Analysis of p53 Gene Alterations in Cancer: A Critical View.- Patterns of TP53 Mutations in Human Cancer: Interplay Between Mutagenesis, DNA Repair and Selection.- Prognostic and Predictive Value of TP53 Mutations in Human Cancer.- P53 Links Tumor Development to Cancer Therapy.- Novel p53-Based Therapies: Strategies and Future Prospects.- Wild Type p53 Conformation, Structural Consequences of p53 Mutations and Mechanisms of Mutant p53 Rescue.- Mutant p53 Reactivation as a Novel Strategy for Cancer Therapy.- Novel Approaches to p53-Based Therapy: ONYX-015.- p53 as Seen by an Outsider.