USP47 promotes tumorigenesis by negative regulation of P53 through deubiquitinating ribosomal protein S2

Jinhong Cho, Jinyoung Park, Sang Chul Shin, Mihue Jang, Jae Hong Kim, Eunice Eunkyeong Kim, Eun Joo Song

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


p53 is activated in response to cellular stresses such as DNA damage, oxidative stress, and especially ribosomal stress. Although the regulations of p53 by E3 ligase and deubiquitinating enzymes (DUBs) have been described, the cellular roles of DUB associated with ribosomal stress have not been well studied. In this study, we report that Ubiquitin Specific Protease 47 (USP47) functions as an important regulator of p53. We show that ubiquitinated ribosomal protein S2 (RPS2) by Mouse double minute 2 homolog (MDM2) is deubiquitinated by USP47. USP47 inhibits the interaction between RPS2 and MDM2 thereby alleviating RPS2-mediated suppression of MDM2 under normal conditions. However, dissociation of USP47 leads to RPS2 binding to MDM2, which is required for the suppression of MDM2, consequently inducing up-regulation of the p53 level under ribosomal stress. Finally, we show that depletion of USP47 induces p53 and therefore inhibits cell proliferation, colony formation, and tumor progression in cancer cell lines and a mouse xenograft model. These findings suggest that USP47 could be a potential therapeutic target for cancer.

Original languageEnglish
Article number1137
Issue number5
Publication statusPublished - 2020 May

Bibliographical note

Funding Information:
Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (2017R1A2B3007224 and 2019R1A2C2004052) and the R&D Convergence Program of NST (National Research Council of Science & Technology) of Republic of Korea (CAP-16-03-KRIBB).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • MDM2
  • P53
  • RPS2
  • Ribosomal stress
  • USP47

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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