Modes of p53 Regulation

By J. Kruse, W. Gu. Cell, 2009

1,601 citations recorded by the source corpus.

The traditional view of p53 activation includes three steps—p53 stabilization, DNA binding, and transcriptional activation. However, recent studies indicate that each step of p53 activation is more complex than originally anticipated. Moreover, both genetic studies in mice and in vitro studies with purified components suggest that the classical model may not be sufficient to explain all aspects of p53 activation in vivo. To reconcile these differences, we propose that antirepression, the release of p53 from repression by factors such as Mdm2 and MdmX, is a key step in the physiological activation of p53.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/8c007674a418616703a1bd9866e886e1d1226133

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In Cancer Research

1. Scott W. Lowe
2. Angus I. Lamond
3. T. Seyfried
4. Laura M. Shelton

In Molecular Biology

1. Scott W. Lowe
2. Angus I. Lamond
3. T. Seyfried
4. Laura M. Shelton
5. J. Campisi
6. Tom Misteli

In Oncology

1. Scott W. Lowe
2. T. Seyfried
3. Laura M. Shelton
4. J. Campisi

Citations in the corpus

• The Nucleolus under Stress (2010, background): “p53 levels are kept low under normal physiological conditions due to its interactions with E3 ubiquitin ligases, the best-studied of which is Hdm2 (also called Mdm2 in mouse), resulting in p53 nuclear export (following monoubiquitinylation), degradation (following polyubiquitinylation), and/or inhib”
• Tumor suppression in the absence of p53-mediated cell cycle arrest, apoptosis, and senescence (2012, neutral): “In broad terms, p53 activities are controlled via protein levels, coactivator/corepressor recruitment, and a diverse array of posttranslational modifications that include acetylation, ubiquitination, phosphorylation, methylation, SUMOylation, and neddylation (Kruse and Gu, 2009).”
• Cancer as a metabolic disease (2010, background): “The cancer mutator phenotype was invoked to explain the large number of somatic mutations found in cancer, but mutations in the p53 caretaker gene are not expressed in all cancers nor does p53 deletion produce cancer in mice suggesting a more complicated involvement of this and other genome guardian”
• Tumor suppressive functions of p53. (2009, background): “Numerous posttranslational modifications of p53 at various amino acids have been described, including phosphorylation, ubiquitination, acetylation, methylation, sumoylation, neddylation, glycosylation, and ribosylation (Carter and Vousden 2009; Kruse and Gu 2009).”