Skp2 binds the cysteine-histidine-rich (CH1 and CH3) domains of p300 that normally mediate p53 association, thereby blocking the p300-p53 interaction, suppressing p53 K382 acetylation and reducing the transactivation of both apoptotic and cell cycle arrest targets in various cancer cells following DNA damage [207]. The gene discussed is EP300; the disease is cancer.