New developments in the multi-site phosphorylation and integration of stress signalling at p53.

New developments in the multi-site phosphorylation and integration of stress signalling at p53.
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p53 多位点磷酸化和应激信号整合的新进展。

DOI:
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发表时间:
1998
影响因子:
2.6
通讯作者:
D. Meek
D. Meek
中科院分区:
医学3区
文献类型:
--
作者:
D. Meek

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目的 综述近年来对p53肿瘤抑制蛋白多位点磷酸化介导应激信号整合的研究进展。 结果 p53蛋白在对一系列细胞应激反应中起关键作用,包括可以损伤DNA的试剂;因此,p53参与感知这些效应对于预防肿瘤发展至关重要。p53是一种有效的但潜伏的转录因子,其可被一系列细胞应激激活,导致细胞生长停滞的诱导或通过细胞凋亡的受控细胞去除。因此,p53受到严格控制,并受到包括多位点磷酸化在内的几个水平的调节。最近的证据表明,不同类型的应激(如电离辐射、紫外线和有丝分裂纺锤体损伤)导致p53的活化与个别磷酸化事件有关。 结论 现在,p53蛋白作为压力信号的整合点的图片正在出现。不同的信号冲击蛋白质的不同结构域,并可能在调节p53反应的类型中合作,这取决于传入信号的性质。
PURPOSE To summarize recent progress in the understanding of the role of multi-site phosphorylation in mediating the integration of stress signals at the p53 tumour suppressor protein. RESULTS The p53 protein plays a key role in the response to a range of cellular stresses including agents that can damage DNA; consequently the involvement of p53 in sensing these effects is central to the prevention of tumour development. p53 is a potent but latent transcription factor that can be activated by a range of cellular stresses leading to the induction of cellular growth arrest or controlled cell removal through apoptosis. Accordingly, p53 is under tight control and is subject to several levels of regulation including multi-site phosphorylation. Recent evidence has implicated individual phosphorylation events in the activation of p53 by different types of stress (e.g. ionizing radiation, UV and mitotic spindle damage). CONCLUSIONS A picture is now emerging of the p53 protein as an integration point for stress signals. Different signals impinge on different domains of the protein and may cooperate in modulating the type of p53 response, depending on the nature of the incoming signal.
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