Issues

Although oncogenic signaling is required for tumorigenesis, it paradoxically can induce oncogene-induced senescence (OIS). How tumors bypass OIS and progress is poorly understood. In their study on page 770, Dutchak and colleagues employed a myristoylated kinase/kinase regulator screen in an in vitro OIS model and found that kinase regulator Mps-one binder co-activator 3A (MOB3A) promotes proliferation despite constitutive BRAF signaling that otherwise induces OIS. The authors went on to demonstrate that MOB3A subverts OIS by deactivating Hippo pathway signaling and inducing YAP/TAZ-mediated transcriptional activation. The cover depicts a merged immunofluorescent image of HEK-293T cells transfected with myristoylated MOB3A, where MOB3A fluoresces green, YAP/TAZ fluoresces red, and nuclei fluoresce blue. MOB3A-induced YAP/TAZ nuclear localization causes nuclei to fluoresce light blue in the merged image. The authors went on to show that shRNA-mediated MOB3A silencing slows tumor growth in vivo, presenting MOB3A as a novel potential therapeutic target. This article is also Highlighted on page 671.