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USP19 Negatively Regulates p53 and Promotes Cervical Cancer Progression

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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.

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Acknowledgements

We would like to thank all the members of the Suri Lab and KSK Lab. We would also like to thank Professor Ryu Seong Eon, Hanyang University, Seoul, South Korea for his help in recombinant protein purification.

Funding

This research was supported by the National Research Foundation of Korea (NRF) grants (2021M3A9H3015389 and 2021R1I1A1A01052637), a Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government (Ministry of Science and ICT, Ministry of Health & Welfare) (22A0304L1-01) and Medical Research Center (2017R1A5A2015395), funded by the National Research Foundation of Korea (NRF) of the Ministry of Science, ICT and Future Planning, Korea.

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Authors and Affiliations

  1. Graduate School of Biomedical Science and Engineering, Hanyang University, 04763, Seoul, South Korea

    Apoorvi Tyagi, Janardhan Keshav Karapurkar, Jencia Carminha Colaco, Neha Sarodaya, Ainsley Mike Antao, Kamini Kaushal, Arun Pandian Chandrasekaran, Soumyadip Das, Bharathi Suresh, Kye-Seong Kim & Suresh Ramakrishna

  2. Department of Life Science, College of Natural Sciences, Hanyang University, 04763, Seoul, South Korea

    Saba Haq

  3. Department of Biosciences, School of Science, Rajpur, Indrashil University, 382715, Mehsana, Gujarat, India

    Vijai Singh

  4. Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea

    Seok-Ho Hong

  5. College of Medicine, Hanyang University, 04763, Seoul, South Korea

    Kye-Seong Kim & Suresh Ramakrishna

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  1. Apoorvi Tyagi
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Contributions

A.T., J.K.K, and S.R.K. designed the study. A.T, J.K.K, and J.C.C conducted experiment and analyzed and interpreted the data. A.T. and S.R.K. co-wrote the manuscript. J.C.C. conducted all revision experiment. B.S., N.S., A.M.A., K.K., S.H., A.P.C., S.D., and V.S. assisted A.T with the experiments. B.S., K.S.K., and S.R. procured financial support and reviewed the manuscript.

Corresponding authors

Correspondence to Bharathi Suresh or Kye-Seong Kim.

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The authors have no competing interests regarding the content of this manuscript to declare.

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This study was approved by the Hanyang University Institutional Review Board (approval number HYI-17-137-10).

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Tyagi, A., Karapurkar, J.K., Colaco, J.C. et al. USP19 Negatively Regulates p53 and Promotes Cervical Cancer Progression. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00814-y

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