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Tumor suppressor Parkin induces p53-mediated cell cycle arrest in human lung and colorectal cancer cells

  • Byung Chul Jung (Department of Nutritional Sciences and Toxicology, University of California ) ;
  • Sung Hoon Kim (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) ;
  • Yoonjung Cho (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University) ;
  • Yoon Suk Kim (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University)
  • Received : 2023.07.26
  • Accepted : 2023.08.28
  • Published : 2023.10.31
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Abstract

Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

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References

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