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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells

  • Yong-Kyu Lee (Department of Integrative Bioscience and Biotechnology, Sejong University) ;
  • Hyeon Ho Heo (Department of Integrative Bioscience and Biotechnology, Sejong University) ;
  • Nackhyoung Kim (Department of Integrative Bioscience and Biotechnology, Sejong University) ;
  • Ui-Hyun Park (Department of Integrative Bioscience and Biotechnology, Sejong University) ;
  • Hyesook Youn (Department of Integrative Bioscience and Biotechnology, Sejong University) ;
  • Eun-Yi Moon (Department of Integrative Bioscience and Biotechnology, Sejong University) ;
  • Eun-Joo Kim (Department of Molecular Biology, Dankook University) ;
  • Soo-Jong Um (Department of Integrative Bioscience and Biotechnology, Sejong University)
  • Received : 2023.12.26
  • Accepted : 2024.04.23
  • Published : 2024.06.30
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Abstract

Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activation-mediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells.

Keywords

Acknowledgement

This study was supported by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2021R1A4A5033289), and also supported by Korea Basic Science Institute (National research Facilities and Equipment Center) grant funded by the Ministry of Education (2023R1A6C101A045).

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