Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15784, Greece.
J Proteomics. 2013 Oct 30;92:274-98. doi: 10.1016/j.jprot.2013.02.024. Epub 2013 Mar 14.
Organisms are constantly challenged by stressors and thus the maintenance of biomolecules functionality is essential for the assurance of cellular homeostasis. Proteins carry out the vast majority of cellular functions by mostly participating in multimeric protein assemblies that operate as protein machines. Cells have evolved a complex proteome quality control network for the rescue, when possible, or the degradation of damaged polypeptides. Nevertheless, despite these proteostasis ensuring mechanisms, new protein synthesis, and the replication-mediated dilution of proteome damage in mitotic cells, the gradual accumulation of stressors during aging (or due to lifestyle) results in increasingly damaged proteome. Non-enzymatic post-translational protein modifications mostly arise by unbalanced redox homeostasis and/or high glucose levels and may cause disruption of proteostasis as they can alter protein function. This outcome may then increase genomic instability due to reduced fidelity in processes like DNA replication or repair. Herein, we present a synopsis of the major non-enzymatic post-translation protein modifications and of the proteostasis network deregulation in carcinogenesis. We propose that activation of the proteostasis ensuring mechanisms in premalignant cells has tumor-preventive effects, whereas considering that over-activation of these mechanisms represents a hallmark of advanced tumors, their inhibition provides a strategy for the development of anti-tumor therapies. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine.
生物体会不断受到应激源的挑战，因此生物分子功能的维持对于确保细胞内稳态至关重要。蛋白质通过参与大多数作为蛋白质机器的多聚体蛋白组装来执行绝大多数细胞功能。细胞已经进化出了一种复杂的蛋白质质量控制网络，以在可能的情况下拯救或降解受损的多肽。然而，尽管有这些蛋白质稳态保障机制、新的蛋白质合成以及有丝分裂细胞中蛋白质组损伤的复制介导稀释，在衰老过程中（或由于生活方式），应激源的逐渐积累导致蛋白质组逐渐受损。非酶翻译后蛋白质修饰主要是由于氧化还原平衡失调和/或高葡萄糖水平引起的，并且可能导致蛋白质稳态失调，因为它们可以改变蛋白质的功能。这种结果可能会由于 DNA 复制或修复等过程的保真度降低而导致基因组不稳定增加。在此，我们总结了主要的非酶翻译后蛋白质修饰以及蛋白质稳态网络在癌变中的失调。我们提出，在癌前细胞中激活蛋白质稳态保障机制具有肿瘤预防作用，而考虑到这些机制的过度激活是晚期肿瘤的标志，抑制这些机制为开发抗肿瘤治疗策略提供了一种方法。本文是题为“生物学和医学中的翻译后蛋白质修饰”的特刊的一部分。
