Ubiquitylation is a post-translational modification that alters PTEN activity, and in melanoma, the neural precursor cell expressed by the developmentally downregulated gene 4-1 (NEDD4-1) E3 ligase forms a covalent bond with lysine11 and lysine48 of the PTEN promoter, resulting in the inactivation of PTEN activity through proteasomal degradation [28]. The gene discussed is PTEN; the disease is melanoma.