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The guardian of the genome: p53 tumor suppressor protein—its role and regulation. When activated on DNA damage, the p53 protein may mediate cell
cycle arrest, DNA repair, and apoptosis. When inducing these effects, p53 acts chiefly as a transcription factor that can activate the transcription of most
target genes, while repressing some of others, such as those marked with (–) in the figure (Liu and Chen, 2006). For example, p53 transactivates p21 and
gadd45 genes (whose products are inhibitors of cyclin–cyclin-dependent protein kinase complexes) and arrest the cell cycle in G1 and G2 phases,
respectively, but p53 represses the Cdk1 and cyclin B1 genes (whose products are indispensable for the cells to transit from G2 phase to M) (see Fig. 325). p53 also induces the expression of miR-34 (a microRNA), which in turn represses the translation of cyclin D, CDK4/6, and E2F, important cell cycle
Source: Mechanisms of Toxicity, Casarett and Doull's Toxicology: The Basic Science of Poisons, 8e
accelerator proteins (see Fig. 3-32) (Chen et al., 2010). p53 also transactivates the genes of some DNA repair proteins and proapoptotic proteins (eg, bax
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p53-induced proapoptotic mechanisms may be cell-specific, that is, all are not necessarily occurring in the same cell at the same time.
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The intracellular level and activity of p53 depends primarily on the presence of mdm2 protein, which inactivates p53 by ubiquitinating it;
monoubiquitination causes export of p53 from the nucleus, whereas polyubiquitination promotes its proteasomal degradation. The influence of mdm2 on