Besides cullin proteins, other important targets for NEDDylation, in the context of osteosarcoma, are p53 (NEDDylated by MDM2) [150], PTEN, which if NEDDylated can contribute to tumorigenesis [151], and SMURF1-2 that upon NEDDylation, are able to increase their E3 ligase activity that, as reported earlier in this review, inhibits osteosarcoma cell growth [152]. Here, MDM2 is linked to osteosarcoma.