文章：

SUMO与癌症的稳健性

SUMO and the robustness of cancer

原文发布日期：2017-01-30

DOI: 10.1038/nrc.2016.143

类型: Review Article

开放获取: 否

要点：

1. Reversible post-translational protein modification by small ubiquitin-like modifier (SUMO), sumoylation, is a crucial mechanism in the maintenance of genomic integrity, in the regulation of proper gene expression patterns and in numerous signal transduction pathways and is thus essential for cell and tissue homeostasis in all eukaryotes.
2. Numerous protein complexes contain multiple sumoylated proteins, suggesting that sumoylation regulates not only the activity of individual substrates but that of entire functional complexes. Furthermore, in complex signalling pathways, sumoylation frequently targets multiple elements, in some cases antagonizing the activity of one element while promoting that of another within the same pathway.
3. Various biotic and abiotic stresses substantially alter the level of global cellular sumoylation. Importantly, numerous human tumours display marked upregulation of SUMO pathway components. This 'SUMOness' of cancers may indeed be required by tumour cells to maintain the robustness of compromised or otherwise easily misregulated gene expression programmes and signalling pathways. Sumoylation would therefore contribute substantially to cancer cell survival and proliferation in a potentially hostile microenvironment.
4. Although strong inhibition of global cellular sumoylation carries obvious risks for all cells, partial or temporary inhibition may be sufficient to expose certain tumour-specific vulnerabilities (for example, susceptibility to inducers of apoptosis and/or senescence) and therefore could provide a promising approach for future therapeutic intervention in some settings.

要点翻译：

1. 可逆的翻译后蛋白质修饰——小泛素样修饰蛋白（SUMO）介导的类泛素化，是维持基因组完整性、调控正确基因表达模式以及众多信号转导通路的关键机制，因此对所有真核生物的细胞和组织稳态至关重要。
2. 多种蛋白质复合物含有多个类泛素化修饰蛋白，表明类泛素化不仅调控单个底物的活性，还调控整个功能复合物的活性。此外，在复杂的信号通路中，类泛素化经常靶向多个元素，有时在同一通路内拮抗一个元素的活性，同时促进另一个元素的活性。
3. 各种生物和非生物胁迫显著改变全局细胞类泛素化水平。重要的是，许多人类肿瘤显示SUMO通路组分显著上调。这种癌症的“SUMO特性”可能确实是肿瘤细胞所需要的，以维持受损或易失调的基因表达程序和信号通路的稳健性。因此，类泛素化在癌细胞在潜在恶劣微环境中的生存和增殖中发挥重要作用。
4. 尽管强力抑制全局细胞类泛素化对所有细胞都有明显风险，但部分或临时抑制可能足以暴露某些肿瘤特异性脆弱点（例如，对凋亡和/或衰老诱导剂的敏感性），因此可能为未来在某些情况下的治疗干预提供有前景的方法。

英文摘要：

Post-translational protein modification by small ubiquitin-like modifier (SUMO), termed sumoylation, is an important mechanism in cellular responses to stress and one that appears to be upregulated in many cancers. Here, we examine the role of sumoylation in tumorigenesis as a possibly necessary safeguard that protects the stability and functionality of otherwise easily misregulated gene expression programmes and signalling pathways of cancer cells.

摘要翻译： 

小泛素样修饰蛋白（SUMO）对蛋白质的翻译后修饰，称为SUMO化，是细胞应对应激的重要机制之一，并且在多种癌症中表现出上调。在此，我们探讨SUMO化在肿瘤发生中的作用，认为它可能是一种必要的保护机制，用以维护癌细胞中本易失控的基因表达程序及信号通路的稳定性与功能。

原文链接：

SUMO and the robustness of cancer