BHLHE40/DEC1 stability is controlled through SCFβTrCP, which mediates the ubiquitin-proteasome system dependent on the phosphorylation of BHLHE40/DEC1 by casein kinase I. BHLHE40/DEC1 protein increases by suppressing ubiquitination in an ATM/ATR-dependent manner by USP17 ubiquitin protease, after exposure to anticancer agents, etoposide or doxorubicin, in huma osteosarcoma U2OS cells and huma colon cancer HCT116 cells, both of which have wt TP53 [46]. This evidence concerns the gene BHLHE40 and osteosarcoma.