mTORC1 and p53 Clash of the gods?
mTORC1 and p53 Clash of the gods?
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DOI：
10.4161/cc.22912
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发表时间：
2013-01-01
期刊：
影响因子：
4.3
通讯作者：
Campisi, Judith
中科院分区：
文献类型：
--
作者：
Hasty, Paul;Sharp, Zelton Dave;Campisi, Judith
必须在细胞生长和应激反应之间取得平衡，以确保细胞在不积累受损DNA的情况下增殖。这种平衡意味着最佳的细胞增殖需要整合促生长和应激反应途径。MTOR(雷帕霉素的机制靶点)是在化合物1(MTORC1)中发现的一种多效性激酶。MTORC1途径调控对高能有丝分裂信号的反应，促进蛋白质合成和细胞生长。相反，P53 DNA损伤反应通路是细胞增殖的仲裁者，在基因毒性应激条件下抑制mTORC1。最近的研究表明，这些途径的复杂整合可以确保细胞在不影响基因组维护的情况下成功生长和增殖。破译这种整合可能是了解雷帕霉素等mTORC1抑制剂潜在临床用途的关键。在这里，我们讨论这些P53-mTORC1相互作用如何在抑制癌症中发挥作用，也许在细胞衰老和生物衰老的发展中发挥作用。
A balance must be struck between cell growth and stress responses to ensure that cells proliferate without accumulating damaged DNA. This balance means that optimal cell proliferation requires the integration of pro-growth and stress-response pathways. mTOR (mechanistic target of rapamycin) is a pleiotropic kinase found in complex 1 (mTORC1). The mTORC1 pathway governs a response to mitogenic signals with high energy levels to promote protein synthesis and cell growth. In contrast, the p53 DNA damage response pathway is the arbiter of cell proliferation, restraining mTORC1 under conditions of genotoxic stress. Recent studies suggest a complicated integration of these pathways to ensure successful cell growth and proliferation without compromising genome maintenance. Deciphering this integration could be key to understanding the potential clinical usefulness of mTORC1 inhibitors like rapamycin. Here we discuss how these p53-mTORC1 interactions might play a role in the suppression of cancer and perhaps the development of cellular senescence and organismal aging.