MDM4 and brain neoplasm: We previously showed that CEP-1347 increased p53 expression in malignant brain tumor cells with the wild-type p53 gene by suppressing the expression of MDM4, one of the negative regulators of p53 [23,24], while IR reportedly down-regulated the expression of MDM4 by phosphorylating MDM4 through the activation of the ATM-Chk2 pathway [13].