A few reports have implicated genetic alterations in CUL5 in cancer progression and our unbiased screens reveal that the CUL5-RNF7-UBE2F ubiquitin ligase can modulate the apoptotic threshold of LK2 cells in response to multiple emerging cancer therapeutics (Burnatowska-Hledin et al., 2004; Fay et al., 2003; Lubbers et al., 2011; Xu et al., 2012). The gene discussed is RNF7; the disease is cancer.