CREB represses p53-dependent transactivation of MDM2 through the complex formation with p53 and contributes to p53-mediated apoptosis in response to glucose deprivation.

Recently, we have described that CREB (cAMP-responsive element-binding protein) has the ability to transactivate tumor suppressor p53 gene in response to glucose deprivation. In this study, we have found that CREB forms a complex with p53 and represses p53-mediated transactivation of MDM2 but not of p21(WAF1). Immunoprecipitation analysis revealed that CREB interacts with p53 in response to glucose deprivation.

MDM2 promotes the proteasomal degradation of p73 through the interaction with Itch in HeLa cells.

It has been shown that MDM2 inhibits the transcriptional and pro-apoptotic activities of p73 but does not promote its proteasomal degradation. In this study, we found that MDM2 indirectly induces the degradation of p73 through the interaction with Itch in HeLa cells. During adriamycin (ADR)-mediated apoptosis, p53 and p73 were induced to stabilize in association with a significant reduction of MDM2 and Itch, suggesting that, in addition to Itch, MDM2 could also be involved in the stability control of p73.