Keeping p53 in Check: A High-Stakes Balancing Act

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Keeping p53 in Check: A High-Stakes Balancing Act Shelley L. Berger  Cell  Volume 142, Issue 1, Pages 17-19 (July 2010) DOI: 10.1016/j.cell.2010.06.026 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 Posttranslational Modifications Regulate p53 Activity The tumor suppressor p53 is a modular protein that contains (from the amino to the carboxyl terminus) two tandem activation domains (green), a DNA binding domain (tan), and an oligomerization domain surrounded by regulatory domains (red). Levels of p53 increase transiently during the normal cell cycle (Loewer et al., 2010). However, the activity of p53 during these bursts is kept in check by methylation (red hexagons) of lysine residues (K370, K373, and K382) in the carboxyl terminus region. In contrast, dimethylation of K370 and monomethylation of K372 activate p53 (Huang and Berger, 2008). In response to DNA damage, sequential regulatory steps occur. The p53 protein is phosphorylated (not shown) and acetylated at multiple sites (K120, K164, K320, K370, and K382). The level of p53 increases in the cell, triggering factors that repair the DNA and arrest the cell cycle. For cell division to resume, the stress response mediated by p53 needs to be attenuated by deacetylation (not shown) and ubiquitin-mediated degradation of p53. Cell 2010 142, 17-19DOI: (10.1016/j.cell.2010.06.026) Copyright © 2010 Elsevier Inc. Terms and Conditions