Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 430, Issue 3, Pages 1034-1039Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.11.121
Keywords
DnaJC7; MDM2; P53; Protein stability; TPR2; Two-hybrid
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Hamaguchi Foundation
- Grants-in-Aid for Scientific Research [23501278] Funding Source: KAKEN
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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. (C) 2012 Elsevier Inc. All rights reserved.
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