CDK4 and osteosarcoma: [43]. Expression of MDM2 is known to inhibit TP53 transcriptional activation [55]. Thus, differential expression of CDC5L, MDM2, and CDK4 could contribute to variation in cellular proliferation during osteosarcoma pathogenesis, especially when there is reduced expression of the tumor suppressors RB1 and TP53, or the TP53 target CDKN1A.