Abstract
Tripartite motif-containing 28 (TRIM28) is an E3 ubiquitin ligase harboring multiple cellular functions. We found that the TRIM28 protein is frequently overexpressed in patients with lung cancer. The stable overexpression of TRIM28 in lung cancer cells and xenograft models significantly increased the proliferation, migration, and invasiveness, whereas knockdown of TRIM28 had the opposite effect. We further observed that TRIM28 regulates the ubiquitin ligases RLIM and MDM2 to target the p53 levels during lung tumorigenesis. These data provide new insights into lung cancer development and potential new therapeutic targets for this disease.
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Acknowledgements
The authors thank the Optical Imaging and Optical Microscopy Cores at the Convergence Medicine Research Center (CREDIT), Asan Medical Center, for support and instruments.
Funding
This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MIST) (2019R1A2C2084181, 2020R1A4A1016029).
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J.J., G.L., S.N., T.L., D.K., and J.Y. conceived and designed analysis; J.J., G.L., and P.L. performed development of methodology and writing, review and revision of the paper. All authors read and approved the final paper.
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Written informed consent was obtained from all the patients with lung cancer who participated in this study. All experimental protocols were approved by the Institutional Review Board of Asan Medical Center and the University of Ulsan College of Medicine (2014-0960, 2020-1117). The study was performed in accordance with the Declaration of Helsinki.
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Jin, JO., Lee, G.D., Nam, S.H. et al. Sequential ubiquitination of p53 by TRIM28, RLIM, and MDM2 in lung tumorigenesis. Cell Death Differ 28, 1790–1803 (2021). https://doi.org/10.1038/s41418-020-00701-y
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DOI: https://doi.org/10.1038/s41418-020-00701-y
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