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

Chen,De-Yu; Dai,Dong-Fang; Hua,Ye; Qi,Wen-Qing

doi:10.3892/ijo.2014.2740

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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Affiliations: Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
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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