MDM4 and cancer: Although stress signals (Palmero et al., 1998; Shieh et al., 1997; Tang et al., 2008; Zhang et al., 1998; Zindy et al., 1998) (Zhang and Lu, 2009; Zhou et al., 2012, 2015a) have been shown to compromise MDM2-induced ubiquitination and proteolysis of p53 and thus activate p53 in normal cells, cancer cells employ oncogenic molecules, such as MDMX (Gembarska et al., 2012; Lam et al., 2010; Slack et al., 2005; Wade et al., 2013), which strengthen MDM2-mediated inhibition of p53 and thus induce cell resistance to p53 activation.