Lessons from interconnected ubiquitylation and acetylation of p53: think metastable networks
Lessons from interconnected ubiquitylation and acetylation of p53: think metastable networks
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DOI：
10.1042/bst0380098
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发表时间：
2010-02-01
影响因子：
3.9
通讯作者：
Coux, Olivier
中科院分区：
文献类型：
--
作者：
Benkirane, Monsef;Sardet, Claude;Coux, Olivier
关键的肿瘤抑制因子p53在DNA损伤和更普遍的遗传毒性应激反应中起着重要作用。其表达和功能的调节受到非常严格的控制，特别是涉及一组极其复杂的翻译后修饰，这要归功于各种“修饰剂”，包括泛素化E3和乙酰转移酶，它们微调蛋白质的稳定性和活性。过去几年的研究表明，除了靶向p53，这些修饰剂还相互修饰，形成了一个复杂的调控分子和事件网络，必须考虑到理解p53调控。我们建议，该网络允许亚稳态平衡，赋予p53通路的敏感性和鲁棒性，这两个属性允许该通路分别回答各种刺激，并在刺激消失时返回到其初始阶段。
The critical tumour suppressor p53 plays a major role in response to DNA damage and, more generally, to genotoxic stress. The regulation of its expression and functions is under very tight controls, and involves, in particular, an extremely complex set of post-translational modifications, thanks to a variety of 'modifiers', including ubiquitylation E3s and acetyltransferases, that fine-tune the stability and activity of the protein. Work of the last few years has revealed that, in addition to targeting p53, these modifiers also modify each other, forming an intricate network of regulatory molecules and events that must be taken into account to understand p53 regulation. We propose that this network allows a metastable equilibrium that confers both sensitivity and robustness on the p53 pathway, two properties that allow the pathway to respectively answer to a variety of stimuli and return to its initial stage when the stimuli disappear.