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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect
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Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect

机译：p53靶基因Parkin介导p53在葡萄糖代谢和Warburg效应中的作用

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摘要

Regulation of energy metabolism is a novel function of p53 in tumor suppression. Parkin (PARK2), a Parkinson disease-associated gene, is a potential tumor suppressor whose expression is frequently diminished in tumors. Here Parkin was identified as a p53 target gene that is an important mediator of p53's function in regulating energy metabolism. The human and mouse Parkin genes contain functional p53 responsive elements, and p53 increases the transcription of Parkin in both humans and mice. Parkin contributes to the function of p53 in glucose metabolism; Parkin deficiency activates glycolysis and reduces mitochondrial respiration, leading to the Warburg effect. Restoration of Parkin expression reverses the Warburg effect in cells. Thus, Parkin deficiency is a novel mechanism for the Warburg effect in tumors. Parkin also contributes to the function of p53 in antioxidant defense. Furthermore, Parkin deficiency sensitizes mice to γ-irra-diation-induced tumorigenesis, which provides further direct evidence to support a role of Parkin in tumor suppression. Our results suggest that as a novel component in the p53 pathway. Parkin contributes to the functions of p53 in regulating energy metabolism, especially the Warburg effect, and antioxidant defense, and thus the function of p53 in tumor suppression.
机译：能量代谢的调节是p53在肿瘤抑制中的新功能。帕金森病（Parkinson disease）相关基因Parkin（PARK2）是一种潜在的抑癌基因，其在肿瘤中的表达经常减少。在这里，帕金被确定为p53靶基因，是p53在调节能量代谢中功能的重要介体。人和小鼠的帕金基因包含功能性p53响应元件，而p53增加人和小鼠中帕金的转录。 Parkin有助于p53在葡萄糖代谢中的功能；帕金菌缺乏会激活糖酵解并减少线粒体呼吸，从而导致Warburg效应。 Parkin表达的恢复逆转了细胞中的Warburg效应。因此，帕金缺乏症是在肿瘤中产生沃伯格效应的新机制。帕金也有助于p53在抗氧化防御中的功能。此外，帕金缺乏症使小鼠对由γ-激怒扩张引起的肿瘤发生敏感，这提供了进一步的直接证据来支持帕金在肿瘤抑制中的作用。我们的结果表明，它是p53途径中的新型成分。帕金有助于p53在调节能量代谢中的功能，特别是Warburg效应和抗氧化防御，从而在抑制肿瘤方面发挥p53的功能。

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    Cen Zhang; Meihua Lin; Rui Wu; Xiaowen Wang; Bo Yang; Arnold J. Levine; Wenwei Hu; Zhaohui Feng;

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    Department of Radiation Oncology , Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903;

    Department of Radiation Oncology , Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903;

    Department of Radiation Oncology , Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903;

    Department of Radiation Oncology , Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903;

    College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;

    Department of Pediatrics, Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903,lnstitute for Advanced Study, Princeton, NJ 08540;

    Department of Pediatrics, Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903;

    Department of Radiation Oncology , Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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