A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration.

The tumor suppressor p53 transactivates the expression of multiple genes to exert its multifaceted functions and ultimately maintains genome stability. Thus, cancer cells develop various mechanisms to diminish p53 expression and bypass the cell cycle checkpoint. In this study, we identified the gene encoding RNA-binding protein cytoplasmic polyadenylation element-binding protein 2 (CPEB2) as a p53 target. In turn, CPEB2 decreases p53 messenger RNA stability and translation to fine-tune p53 level. Specifically, we showed that CPEB2 binds the cytoplasmic polyadenylation elements in the p53 3'-untranslated region, and the RNA recognition motif and zinc finger (ZF) domains of CPEB2 are required for this binding. Furthermore, we found that CPEB2 was upregulated in renal cancer tissues and promotes the renal cancer cell proliferation and migration. The oncogenic effect of CPEB2 is partially dependent on negative feedback regulation of p53. Overall, we identify a novel regulatory feedback loop between p53 and CPEB2 and demonstrate that CPEB2 promotes tumor progression by inactivating p53, suggesting that CPEB2 is a potential therapeutic target in human renal cancer. Copyright © 2021. Published by Elsevier Ltd.

Citation

Jiehui Di, Guang Zhao, Hui Wang, Yaoyao Wu, Zhongjun Zhao, Bao Zhu, Yanping Zhang, Junnian Zheng, Yong Liu, Ying Hu. A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration. Journal of genetics and genomics = Yi chuan xue bao. 2021 Jul 20;48(7):606-617

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PMID: 34362680

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