p53 suppresses 14-3-3γ by stimulating proteasome-mediated 14-3-3γ protein degradation

  • Authors:
    • De-Yu Chen
    • Dong-Fang Dai
    • Ye Hua
    • Wen-Qing Qi
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  • Published online on: November 7, 2014     https://doi.org/10.3892/ijo.2014.2740
  • Pages: 818-824
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Abstract

14-3-3 proteins are a family of highly conserved polypeptides that interact with a large number of proteins and play a role in a wide variety of cellular processes. 14-3-3 proteins have been demonstrated overexpressed in several cancers and serving as potential oncogenes. In a previous study we showed one isoform of the 14-3-3 family, 14-3-3γ was negatively regulated by p53 through binding to its promoter and inhibiting its transcription. In the present study we investigated both p53 and 14-3-3γ protein levels in human lung cancerous tissues and normal lung tissues. We found 14-3-3γ expression correlated to p53 overexpression in lung cancer tissues. Ecotopic expression of wild-type p53, but not mutant p53 (R175H) suppressed both endogenous and exogenous 14-3-3γ in colon and lung cancer cell lines. Further examination demonstrated that p53 interacted with C-terminal domain of 14-3-3γ and induced 14-3-3γ ubiquitination. MG132, a specific inhibitor of the 26S proteasome, could block the effect of p53 on 14-3-3γ protein levels, suggesting that p53 suppressed 14-3-3γ by stimulating the process of proteasome-mediated degradation of 14-3-3γ. These results indicate that the inhibitory effect of p53 on 14-3-3γ is mediated also by a post-transcriptional mechanism. Loss of p53 function may result in upregulation of 14-3-3γ in lung cancers.
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February-2015
Volume 46 Issue 2

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Spandidos Publications style
Chen D, Dai D, Hua Y and Qi W: p53 suppresses 14-3-3γ by stimulating proteasome-mediated 14-3-3γ protein degradation. Int J Oncol 46: 818-824, 2015.
APA
Chen, D., Dai, D., Hua, Y., & Qi, W. (2015). p53 suppresses 14-3-3γ by stimulating proteasome-mediated 14-3-3γ protein degradation. International Journal of Oncology, 46, 818-824. https://doi.org/10.3892/ijo.2014.2740
MLA
Chen, D., Dai, D., Hua, Y., Qi, W."p53 suppresses 14-3-3γ by stimulating proteasome-mediated 14-3-3γ protein degradation". International Journal of Oncology 46.2 (2015): 818-824.
Chicago
Chen, D., Dai, D., Hua, Y., Qi, W."p53 suppresses 14-3-3γ by stimulating proteasome-mediated 14-3-3γ protein degradation". International Journal of Oncology 46, no. 2 (2015): 818-824. https://doi.org/10.3892/ijo.2014.2740