MDM2 Acts Downstream of p53 as an E3 Ligase to Promote FOXO Ubiquitination and Degradation

• Published in: The Journal of biological chemistry Vol. 284; no. 21; pp. 13987 - 14000
• Main Authors: Fu, Wei, Ma, Qiuping, Chen, Lei, Li, Pengfei, Zhang, Mu, Ramamoorthy, Sivapriya, Nawaz, Zafar, Shimojima, Tsukasa, Wang, Hengbin, Yang, Yonghua, Shen, Zheng, Zhang, Yingtao, Zhang, Xiaohong, Nicosia, Santo V., Zhang, Yanping, Pledger, Jack W., Chen, Jiandong, Bai, Wenlong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.05.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Apoptosis; Cell Line; Cell Nucleus - metabolism; Cytoprotection; Forkhead Transcription Factors - metabolism; Gene Expression Regulation; Humans; Mechanisms of Signal Transduction; Mice; Phosphorylation; Protein Binding; Protein Processing, Post-Translational; Protein Transport; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-mdm2 - chemistry; Proto-Oncogene Proteins c-mdm2 - metabolism; Tumor Suppressor Protein p53 - metabolism; Ubiquitin-Protein Ligases - metabolism; Ubiquitination

Members of the FOXO (forkhead O) class of transcription factors are tumor suppressors that also control aging and organismal life span. Mammalian FOXO degradation is proteasome-mediated, although the ubiquitin E3 ligase for FOXO factors remains to be defined. We show that MDM2 binds to FOXO1 and FOX...