https://scholars.lib.ntu.edu.tw/handle/123456789/586017
標題: | CDC25B induces cellular senescence and correlates with tumor suppression in a p53-dependent manner | 作者: | Chen, Ying-Chieh Hsieh, Hsi-Hsien Chang, Hsi-Chi Wang, Hsin-Chiao Lin, Wey-Jinq JING-JER LIN |
關鍵字: | CDC25B; p53; phosphatase; senescence; tumor suppression | 公開日期: | 2021 | 卷: | 296 | 來源出版物: | The Journal of biological chemistry | 摘要: | The phosphatase cell division cycle 25B (Cdc25B) regulates cell cycle progression. Increased Cdc25B levels are often detected in cancer cell lines and human cancers and have been implicated in contributing to tumor growth, potentially by providing cancer cells with the ability to bypass checkpoint controls. However, the specific mechanism by which increased Cdc25B impacts tumor progression is not clear. Here we analyzed The Cancer Genome Atlas (TCGA) database and found that patients with high CDC25B expression had the expected poor survival. However, we also found that high CDC25B expression had a p53-dependent tumor suppressive effect in lung cancer and possibly several other cancer types. Looking in more detail at the tumor suppressive function of Cdc25B, we found that increased Cdc25B expression caused inhibition of cell growth in human normal fibroblasts. This effect was not due to alteration of specific cell cycle stage or inhibition of apoptosis, nor by induction of the DNA damage response. Instead, increased CDC25B expression led cells into senescence. We also found that p53 was required to induce senescence, which might explain the p53-dependent tumor suppressive function of Cdc25B. Mechanistically, we found that the Cdc25B phosphatase activity was required to induce senescence. Further analysis also found that Cdc25B stabilized p53 through binding and dephosphorylating p53. Together, this study identified a tumor-suppressive function of Cdc25B that is mediated through a p53-dependent senescence pathway. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/586017 | ISSN: | 00219258 | DOI: | 10.1016/j.jbc.2021.100564 | SDG/關鍵字: | Cell culture; Cell death; Cell growth; Cell proliferation; Diseases; Phosphatases; Cancer cell lines; Cdc25B phosphatase; Cell division cycle; Cell-cycle progression; Cellular senescence; DNA damage response; Tumor progressions; Tumor suppression; Tumors; cell cycle protein; cell division cycle 25B; protein p53; unclassified drug; protein p53; TP53 protein, human; Article; cancer inhibition; cell aging; controlled study; DNA damage response; enzyme activity; fibroblast; gene overexpression; human; human cell; lung cancer; protein binding; protein expression; protein stability; cell cycle; DNA damage; metabolism; tumor cell line; Cell Cycle; Cell Line, Tumor; Cellular Senescence; DNA Damage; Humans; Tumor Suppressor Protein p53 |
顯示於: | 生物化學暨分子生物學科研究所 |
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