1. USP19 Negatively Regulates p53 and Promotes Cervical Cancer Progression.
- Author
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Tyagi A, Karapurkar JK, Colaco JC, Sarodaya N, Antao AM, Kaushal K, Haq S, Chandrasekaran AP, Das S, Singh V, Hong SH, Suresh B, Kim KS, and Ramakrishna S
- Subjects
- Humans, Female, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Endopeptidases metabolism, Endopeptidases genetics, CRISPR-Cas Systems, HeLa Cells, Cell Proliferation, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms metabolism, Uterine Cervical Neoplasms pathology, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics, Ubiquitination, Cell Movement, Disease Progression
- Abstract
p53 is a tumor suppressor gene activated in response to cellular stressors that inhibits cell cycle progression and induces pro-apoptotic signaling. The protein level of p53 is well balanced by the action of several E3 ligases and deubiquitinating enzymes (DUBs). Several DUBs have been reported to negatively regulate and promote p53 degradation in tumors. In this study, we identified USP19 as a negative regulator of p53 protein level. We demonstrate a direct interaction between USP19 and p53 by pull down assay. The overexpression of USP19 promoted ubiquitination of p53 and reduced its protein half-life. We also demonstrate that CRISPR/Cas9-mediated knockout of USP19 in cervical cancer cells elevates p53 protein levels, resulting in reduced colony formation, cell migration, and cell invasion. Overall, our results indicate that USP19 negatively regulates p53 protein levels in cervical cancer progression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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