Many cancer cells have increased levels of Mcl-1 protein due to the misregulation of cellular UPS factors like MULE, USP9X and components of the SCFFbw7 complex (Schwickart et al., 2010; Zhong et al., 2005; Inuzuka et al., 2011) which promotes apoptosis resistance (Zhang et al., 2002; Adams and Cooper, 2007). Here, HUWE1 is linked to cancer.