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KMID : 0624620230560100557
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BMB Reports
2023 Volume.56 No. 10 p.557 ~ p.562
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Tumor suppressor Parkin induces p53-mediated cell cycle arrest in human lung and colorectal cancer cells
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Abstract
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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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KEYWORD
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Cell cycle arrest, Cyclin B1, DNA damage, p53, Parkin
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