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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53/MDM2 signaling pathway in aging, senescence and tumorigenesis
Youyi Huang1, Xiaofang Che1, Peter W Wang2
1Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Provincial key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Clinical Cancer Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.
Abstract:
A wealth of evidence has emerged that there is an association between aging, senescence and tumorigenesis. Senescence, a biological process by which cells cease to divide and enter a status of permanent cell cycle arrest, contributes to aging and aging-related diseases, including cancer. Aging populations have the higher incidence of cancer due to a lifetime of exposure to cancer-causing agents, reduction of repairing DNA damage, accumulated genetic mutations, and decreased immune system efficiency. Cancer patients undergoing cytotoxic therapies, such as chemotherapy and radiotherapy, accelerate aging. There is growing evidence that p53/MDM2 (murine double minute 2) axis is critically involved in regulation of aging, senescence and oncogenesis. Therefore, in this review, we describe the functions and mechanisms of p53/MDM2-mediated senescence, aging and carcinogenesis. Moreover, we highlight the small molecular inhibitors, natural compounds and PROTACs (proteolysis targeting chimeras) that target p53/MDM2 pathway to influence aging and cancer. Modification of p53/MDM2 could be a potential strategy for treatment of aging, senescence and tumorigenesis.
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