Charni Meital, Aloni-Grinstein Ronit, Molchadsky Alina, Rotter Varda
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Cell Death Differ. 2017 Jan;24(1):8-14. doi: 10.1038/cdd.2016.117. Epub 2016 Oct 21.
Regeneration and tumorigenesis share common molecular pathways, nevertheless the outcome of regeneration is life, whereas tumorigenesis leads to death. Although the process of regeneration is strictly controlled, malignant transformation is unrestrained. In this review, we discuss the involvement of TP53, the major tumor-suppressor gene, in the regeneration process. We point to the role of p53 as coordinator assuring that regeneration will not shift to carcinogenesis. The fluctuation in p53 activity during the regeneration process permits a tight control. On one hand, its inhibition at the initial stages allows massive proliferation, on the other its induction at advanced steps of regeneration is essential for preservation of robustness and fidelity of the regeneration process. A better understanding of the role of p53 in regulation of regeneration may open new opportunities for implementation of TP53-based therapies, currently available for cancer patients, in regenerative medicine.
再生与肿瘤发生共享一些共同的分子途径,然而再生的结果是存活,而肿瘤发生则导致死亡。尽管再生过程受到严格控制,但恶性转化却是不受限制的。在本综述中,我们讨论了主要的肿瘤抑制基因TP53在再生过程中的作用。我们指出p53作为协调者的作用,确保再生不会转变为致癌过程。再生过程中p53活性的波动允许进行严格控制。一方面,其在初始阶段的抑制允许大量增殖,另一方面,其在再生后期阶段的诱导对于维持再生过程的稳健性和准确性至关重要。更好地理解p53在再生调节中的作用可能为将目前癌症患者可用的基于TP53的疗法应用于再生医学开辟新的机会。