核糖体蛋白-MDM2-p53信号通路：连接核糖体生物合成与肿瘤监测
RP-MDM2-p53 Pathway: Linking Ribosomal Biogenesis and Tumor Surveillance.
作者信息
Liu Yong, Deisenroth Chad, Zhang Yanping
机构信息
Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA.
出版信息
Trends Cancer. 2016 Apr;2(4):191-204. doi: 10.1016/j.trecan.2016.03.002. Epub 2016 Apr 4.
Abstract
Ribosomal biogenesis is tightly associated with cellular activities, such as growth, proliferation, and cell cycle progression. Perturbations in ribosomal biogenesis can initiate so-called nucleolar stress. The process through which ribosomal proteins (RPs) transduce nucleolar stress signals via MDM2 to p53 has been described as a crucial tumor-suppression mechanism. In this review we focus on recent progress pertaining to the function and mechanism of RPs in association with the MDM2-p53 tumor-suppression network, and the potential implications this surveillance network has for cancer development.
摘要
核糖体生物合成与细胞活动紧密相关，如生长、增殖和细胞周期进程。核糖体生物合成的扰动可引发所谓的核仁应激。核糖体蛋白（RPs）通过MDM2将核仁应激信号转导至p53的过程已被描述为一种关键的肿瘤抑制机制。在本综述中，我们聚焦于核糖体蛋白在与MDM2-p53肿瘤抑制网络相关的功能和机制方面的最新进展，以及这个监测网络对癌症发展的潜在影响。
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本文引用的文献
1
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J Cancer. 2016 Jan 1;7(1):32-6. doi: 10.7150/jca.13292. eCollection 2016.
2
Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis.成年小鼠中Rpl11部分缺失重现了先天性纯红细胞再生障碍性贫血并促进淋巴瘤发生。
Cell Rep. 2015 Oct 27;13(4):712-722. doi: 10.1016/j.celrep.2015.09.038. Epub 2015 Oct 17.
3
Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation.与RPL11复合的人MDM2结构揭示了p53激活的分子基础。
Genes Dev. 2015 Jul 15;29(14):1524-34. doi: 10.1101/gad.261792.115.
4
Ribosomal Protein Mutations Result in Constitutive p53 Protein Degradation through Impairment of the AKT Pathway.核糖体蛋白突变通过损害AKT途径导致p53蛋白持续性降解。
PLoS Genet. 2015 Jul 1;11(7):e1005326. doi: 10.1371/journal.pgen.1005326. eCollection 2015 Jul.
5
p53 in survival, death and metabolic health: a lifeguard with a licence to kill.p53 在生存、死亡和代谢健康中的作用：有杀人执照的救生员。
Nat Rev Mol Cell Biol. 2015 Jul;16(7):393-405. doi: 10.1038/nrm4007.
6
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Oncogene. 2015 Nov 12;34(46):5709-17. doi: 10.1038/onc.2015.39. Epub 2015 Mar 30.
7
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Cell Rep. 2015 Mar 3;10(8):1310-23. doi: 10.1016/j.celrep.2015.01.055. Epub 2015 Feb 26.
9
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10
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