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

• Published in: Biochemical and biophysical research communications Vol. 406; no. 1; pp. 79 - 84
• Main Authors: Okoshi, Rintaro, Kubo, Natsumi, Nakashima, Kumiko, Shimozato, Osamu, Nakagawara, Akira, Ozaki, Toshinori
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.03.2011
• Subjects: Apoptosis; Cell Line, Tumor; CREB; Cyclic AMP Response Element-Binding Protein - metabolism; Down-Regulation; Glucose - deficiency; Glucose deprivation; Humans; MDM2; p21 WAF1; p53; Protein Structure, Tertiary - genetics; Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors; Proto-Oncogene Proteins c-mdm2 - genetics; Transcriptional Activation; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; MDM2; p21 WAF1; CREB; Glucose deprivation; Apoptosis; p53
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.01.114

► CREB interacts with tumor suppressor p53 in cells. ► CREB/p53 complex preferentially suppresses the transcription of MDM2 gene. ► CREB/p53 complex contributes to glucose deprivation-mediated apoptosis. 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. Forced expression of CREB significantly attenuated the up-regulation of the endogenous MDM2 in response to p53. By contrast, the mutant form of CREB lacking DNA-binding domain (CREBΔ) had an undetectable effect on the expression level of the endogenous MDM2. During the glucose deprivation-mediated apoptosis, there existed an inverse relationship between the expression levels of MDM2 and p53/CREB. Additionally, p53/CREB complex was dissociated from MDM2 promoter in response to glucose deprivation. Collectively, our present results suggest that CREB preferentially down-regulates MDM2 and thereby contributing to p53-mediated apoptosis in response to glucose deprivation.