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Biochem Biophys Res Commun. 2013 Jan 18;430(3):1034-9. doi: 10.1016/j.bbrc.2012.11.121. Epub 2012 Dec 21.

Co-chaperon DnaJC7/TPR2 enhances p53 stability and activity through blocking the complex formation between p53 and MDM2.

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  • 1Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

Abstract

Tumor suppressor p53 plays a critical role in the regulation of DNA damage response. Upon severe DNA damage, p53 promotes apoptosis to eliminate cells with seriously damaged DNA to maintain genomic integrity. Pro-apoptotic function of p53 is tightly linked to its sequence-specific transactivation ability. In the present study, we have identified co-chaperon DnaJC7/TPR2 as a novel binding partner of p53 by yeast-based two-hybrid screening. In the two-hybrid screening, we used the central DNA-binding domain of p53 as a bait. Co-immunoprecipitation experiments demonstrated that DnaJC7 is associated with p53 in mammalian cells. Luciferase reporter and colony formation assays revealed that DnaJC7 enhances p53-dependent transcriptional as well as growth-suppressive activity. Forced expression of DnaJC7 induced to extend a half-life of p53, indicating that DnaJC7-mediated activation of p53 might be at least in part due to its prolonged half-life. Consistent with these observations, the amount of p53/MDM2 complex was markedly reduced in the presence of DnaJC7, suggesting that DnaJC7 dissociates MDM2 from p53. Taken together, our present findings strongly suggest that DnaJC7 participates in p53/MDM2 negative feedback regulatory pathway, and thereby enhancing the stability and activity of p53.

Copyright © 2012 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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