The physiological relevance of the K63-linked ubiquitination of Akt in cancerogenesis is further highlighted by the observation that the constitutively active and cancer-associated Akt E17K mutant is more effectively ubiquitinated by NEDD4-1 and shows a higher basal level of K63-linked ubiquitination than wild-type, thus explaining the increased activity and oncogenic potential of this mutant [54,108,109]. Here, AKT1 is linked to cancer.