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Changing the p53 master regulatory network: ELEMENTary, my dear Mr Watson

Oncogene volume 26, pages 2191–2201 (2007)Cite this article

Abstract

The p53 master regulatory network provides for the stress-responsive direct control of a vast number of genes in humans that can be grouped into several biological categories including cell-cycle control, apoptosis and DNA repair. Similar to other sequence-specific master regulators, there is a matrix of key components, which provide for variation within the p53 master regulatory network that include p53 itself, target response element sequences (REs) that provide for p53 regulation of target genes, chromatin, accessory proteins and transcription machinery. Changes in any of these can impact the expression of individual genes, groups of genes and the eventual biological responses. The many REs represent the core of the master regulatory network. Since defects or altered expression of p53 are associated with over 50% of all cancers and greater than 90% of p53 mutations are in the sequence-specific DNA-binding domain, it is important to understand the relationship between wild-type or mutant p53 proteins and the target response elements. In the words of the legendary detective Sherlock Holmes, it is ‘Element ary, my dear Mr. Watson.’

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Acknowledgements

We appreciate the critical comments on the paper by Chris Halweg and Tom Darden. This work was partially supported by a grant from the Italian Association for Cancer Research, AIRC (to AI) and intramural research funds from NIEHS. Jennifer Jordan is supported by a Department of Defense Breast Cancer Research Program Predoctoral Traineeship Award (BC051212).

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  1. D Menendez, A Inga, J J Jordan and M A Resnick: These two authors equally contributed to this work.

Authors and Affiliations

  1. Laboratory of Molecular Genetics, Chromosome Stability Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA

    D Menendez, J J Jordan & M A Resnick

  2. Department of Translational Oncology, Molecular Mutagenesis Unit, National Institute for Cancer Research, IST, Genoa, Italy

    A Inga

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Menendez, D., Inga, A., Jordan, J. et al. Changing the p53 master regulatory network: ELEMENTary, my dear Mr Watson. Oncogene 26, 2191–2201 (2007). https://doi.org/10.1038/sj.onc.1210277

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