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The p53-ARF-MDM2/4 pathway (adapted from the p53 website) [24]. In response to hyperproliferative stress and/or DNA damage, pathway mediators, such as ARF, are activated. MDM2 and MDM4 mark p53 for degradation, and are subsequently degraded when upstream mediators are activated. This releases p53 from degradation, and leads to increased cell cycle arrest, apoptosis, DNA Repair, and cellular senescence.
