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The p53 gene encodes one of the most important tumor suppressors in human cells and undergoes frequent mutational inactivation in cancers. MDM2, a transcriptional target of p53, binds p53 and can both inhibit p53-mediated transcription [1] [2] and target p53 for proteasome-mediated proteolysis [3] [4]. A close relative of p53, p73, has recently been identified [5] [6]. Here, we report that, like p53, p73alpha and the alternative transcription product p73beta also bind MDM2. Interaction between MDM2 and p53 represents a key step in the regulation of p53, as MDM2 promotes the degradation of p53. In striking contrast to p53, the half-life of p73 was found to be increased by binding to MDM2. Like MDM2, the MDM2-related protein MDMX also bound p73 and stabilized the level of p73. Moreover, the growth suppression functions of p73 and the induction of endogenous p21, a major mediator of the p53-dependent growth arrest pathway, were enhanced in the presence of MDM2. These differences between the regulation of p53 and p73 by MDM2/MDMX may highlight a physiological difference in their action.

Original publication

DOI

10.1016/s0960-9822(99)80367-4

Type

Journal article

Journal

Curr Biol

Publication Date

29/07/1999

Volume

9

Pages

829 - 832

Keywords

Cell Division, Cell Line, DNA-Binding Proteins, Drug Stability, Genes, Tumor Suppressor, Half-Life, HeLa Cells, Humans, In Vitro Techniques, Mutation, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Recombinant Fusion Proteins, Transfection, Tumor Protein p73, Tumor Suppressor Protein p53, Tumor Suppressor Proteins