Sci. STKE, 16 December 2003
UBIQUITINATION Fateful Dose of Mdm2
The p53 tumor suppressor pathway is frequently inactivated in human cancer. In response to stress, the cellular levels of p53 protein rise, which can lead either to cell growth arrest or apoptosis. In normal cells, p53 levels are kept low through rapid protein turnover. This process is tightly regulated by the E3 ubiquitin ligase Mdm2, but experiments aimed at dissecting the mechanistic details have yielded conflicting results. Li et al. now show that the fate of p53 is determined by the level of Mdm2 activity in the cell. Low levels of Mdm2 promote monoubiquitination and nuclear export of p53, whereas high levels of Mdm2 promote its polyubiquitination and degradation in the nucleus.
Citation: Fateful Dose of Mdm2. Sci. STKE 2003, tw490 (2003).
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