MDM2 and osteosarcoma: For instance, in wild type p53-harboring osteosarcoma cell line U2OS, increased expression of NS inhibits MDM2 E3 ligase activity toward p53 and thus activates p53, resulting in G1 cell cycle arrest, while knocking down NS also activates p53 indirectly by causing ribosomal stress that induces the interaction of ribosomal protein L5 and L11 with MDM2 and consequently inhibits MDM2 activity toward p53 [2, 3].