p53—A Natural Cancer Killer: Structural Insights and Therapeutic Concepts
- 29 September 2006
- journal article
- review article
- Published by Wiley in Angewandte Chemie-International Edition
- Vol. 45 (39), 6440-6460
- https://doi.org/10.1002/anie.200600611
Abstract
Every single day, the DNA of each cell in the human body is mutated thousands of times, even in absence of oncogenes or extreme radiation. Many of these mutations could lead to cancer and, finally, death. To fight this, multicellular organisms have evolved an efficient control system with the tumor‐suppressor protein p53 as the central element. An intact p53 network ensures that DNA damage is detected early on. The importance of p53 for preventing cancer is highlighted by the fact that p53 is inactivated in more than 50 % of all human tumors. Thus, for good reason, p53 is one of the most intensively studied proteins. Despite the great effort that has been made to characterize this protein, the complex function and the structural properties of p53 are still only partially known. This review highlights basic concepts and recent progress in understanding the structure and regulation of p53, focusing on emerging new mechanistic and therapeutic concepts.Keywords
This publication has 307 references indexed in Scilit:
- Prospective therapeutic applications of p53 inhibitorsBiochemical and Biophysical Research Communications, 2005
- Mdmx as an essential regulator of p53 activityBiochemical and Biophysical Research Communications, 2005
- Regulation of DNA Binding of p53 by its C-terminal DomainJournal of Molecular Biology, 2004
- Cooperative Binding of Tetrameric p53 to DNAJournal of Molecular Biology, 2004
- Small molecules that reactivate mutant p53European Journal Of Cancer, 2003
- GermlineTP53 mutations and Li-Fraumeni syndromeHuman Mutation, 2003
- Recognition of DNA by p53 Core Domain and Location of Intermolecular Contacts of Cooperative BindingJournal of Molecular Biology, 2002
- Structure and functionality of a designed p53 dimerJournal of Molecular Biology, 2001
- MDM2 — master regulator of the p53 tumor suppressor proteinGene, 2000
- How Phosphorylation Regulates the Activity of p53Journal of Molecular Biology, 1996