Our lab has recently elucidated a novel mechanism of IFN-γ action via ubiquitin proteasomal degradation pathway, mediated by zinc RING finger E3 ubiquitin ligase cullin-5, to facilitate proteasomal degradation of HER2 membrane receptor and improve response in HER2+ breast cancer in vitro and in vivo (114). The gene discussed is ERBB2; the disease is breast carcinoma.