Cancer cell radiosensitization by inactivation of CRL E3: Inactivation of CRL ligase activity by siRNA silencing of its components (e.g., RBX1/RBX2) or by the small-molecule MLN4924 which inhibits cullin neddylation, causes accumulation of CRL substrates. Accumulation of some of these substrates, such as CDT1, WEE1, and p21, leading to altered DNA damage response and G2/M arrest, was found to be causally related to MLN4924-mediated radiosensitization in a cancer cell type-dependent manner.