PMAIP1 and osteosarcoma: Another study showed that the application of sub-toxic concentrations of MLN4924 (0.04, 0.2, or 1 μM) on a human osteosarcoma (OS) cell line, namely SJSA-1, for 6, 24, or 48 h inhibits the neddylation of cullins and blocks the degradation of CRL substrates including CDT1, p27, p21, Wee1, Noxa, p16, and cyclin E associated with cell proliferation and apoptosis.