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Negative regulation of the p300-p53 interplay by DDX24

Oncogene volume 35, pages 528–536 (2016)Cite this article

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Abstract

Numerous studies indicate that p300 acts as a key transcriptional cofactor in vivo, at least, in part, by modulating activities of p53 by acetylation. Nevertheless, the regulation of the p53-p300 interplay is not completely understood. Here, we have identified the DEAD (Asp-Glu-Ala-Asp) box RNA helicase 24 (DDX24) as a novel regulator of the p300-p53 axis. We found that DDX24 interacts with p300, and this interaction leads to suppression of p300-mediated acetylation of p53. Notably, RNA interference-mediated knockdown of endogenous DDX24 significantly increases the acetylation levels of endogenous p53 in human cancer cells and subsequently promotes p53-mediated activation of its transcriptional targets such as p21 and p53 upregulated modulator of apoptosis (PUMA). In contrast, DDX24 expression inhibits the p300-p53 interaction and suppresses p300-mediated acetylation of p53. Moreover, DDX24 is overexpressed in human cancer cells and reduction of DDX24 protein levels by RNA interference induces cell cycle arrest and senescence in a p53-dependent manner. These results reveal DDX24 as an important regulator of p300 and suggest that the modulation of the p53-p300 interplay by DDX24 is critical in controlling p53 activities in human cancer cells.

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Acknowledgements

This work was supported by the National Cancer Institute of the National Institutes of Health under Award 5RO1 CA172023, 5RO1 CA166294, 5RO1CA085533 and 2P01CA080058 to WG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D Shi is also supported by NIH cancer biology training grant T32-CA09503. We especially thank Dr Ruping Sun for his help with the analysis of TCGA database.

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Authors and Affiliations

  1. Department of Pathology and Cell Biology, Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, NY, USA

    D Shi, C Dai & W Gu

  2. Departments of Biochemistry and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA

    J Qin

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Correspondence to W Gu.

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Shi, D., Dai, C., Qin, J. et al. Negative regulation of the p300-p53 interplay by DDX24. Oncogene 35, 528–536 (2016). https://doi.org/10.1038/onc.2015.77

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