Relevance of this regulatory strategy is supported by the existence of a specific cancer-associated mutation (AKT E17K) that displays enhanced ubiquitination and constitutive membrane localization (Fan et al., 2013; Wang et al., 2019), and by the observation that reactivation of AKT through Skp2-mediated ubiquitination plays a role in promoting resistance to PI3K inhibitors in TNBC (Clement et al., 2018). Here, AKT1 is linked to cancer.