Previous studies demonstrated a role for CUL5-based complexes in HSP90-inhibitor-dependent kinase degradation in cancer cells such as HT29 and HCT116 (Ehrlich et al., 2009, Samant et al., 2014) that was surprisingly independent of the TCEB2-TCEB1 (Elongin B-Elongin C) proteins that physically link CUL5 to the SOCS substrate specificity adaptors of that system (Lydeard et al., 2013). The gene discussed is CUL5; the disease is cancer.