Treatment of osteosarcoma cells with the anticancer inhibitor MLN4924 inhibits the degradation of cullins, inducing the accumulation of several tumor-suppressive substrates of cullin-RING E3 ubiquitin ligases (CRLs), including CDT1, Wee1, p21, p27, Noxa, and p16. Here, CDKN1A is linked to osteosarcoma.