p300/MDM2 complexes participate in MDM2-mediated p53 degradation.

Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a ...
naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.
Mesh Terms:
Cell Line, DNA-Binding Proteins, Humans, Molecular Sequence Data, Mutagenesis, Neoplasm Proteins, Nuclear Proteins, Oncogene Proteins, Viral, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Sequence Homology, Amino Acid, Trans-Activators, Tumor Suppressor Protein p53, Ubiquitins
Mol. Cell
Date: Oct. 01, 1998
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