Diversity and versatility of p38 kinase signalling in health and disease.
Diversity and versatility of p38 kinase signalling in health and disease.
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DOI：
10.1038/s41580-020-00322-w
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Nebreda AR
中科院分区：
文献类型：
--
作者：
Canovas B;Nebreda AR
细胞以精确和协调的方式处理不同类型的应激情况的能力是生存的关键，并涉及各种信号网络。在过去的25年里，p38 --尤其是p38-α--在许多水平上参与了细胞对应激的反应。从环境和细胞内应激，如高渗透压、氧化应激或DNA损伤，到涉及重要细胞变化的生理情况，如分化。鉴于p38α控制着过多的功能，这一途径的失调与炎症、免疫紊乱或癌症等疾病有关，这表明靶向p38α可能具有治疗意义。在这篇综述中，我们讨论了这一信号通路的组织，重点是p38α底物的多样性，它们的机制以及它们与特定细胞功能的联系。然后，我们讨论了如何根据接收到的信号和细胞类型产生不同的细胞反应，并强调了这种激酶在人类生理和病理环境中的作用。P38α是p38激酶家族中特征最明确的成员，是细胞应激反应的关键调节因子。P38α被过多的信号和功能激活，通过多种底物调节不同的细胞行为。了解上下文依赖的p38α信号转导有助于深入了解p38α在生理学和病理学中的作用。
The ability of cells to deal with different types of stressful situations in a precise and coordinated manner is key for survival and involves various signalling networks. Over the past 25 years, p38 kinases — in particular, p38α — have been implicated in the cellular response to stress at many levels. These span from environmental and intracellular stresses, such as hyperosmolarity, oxidative stress or DNA damage, to physiological situations that involve important cellular changes such as differentiation. Given that p38α controls a plethora of functions, dysregulation of this pathway has been linked to diseases such as inflammation, immune disorders or cancer, suggesting the possibility that targeting p38α could be of therapeutic interest. In this Review, we discuss the organization of this signalling pathway focusing on the diversity of p38α substrates, their mechanisms and their links to particular cellular functions. We then address how the different cellular responses can be generated depending on the signal received and the cell type, and highlight the roles of this kinase in human physiology and in pathological contexts. p38α — the best-characterized member of the p38 kinase family — is a key mediator of cellular stress responses. p38α is activated by a plethora of signals and functions through a multitude of substrates to regulate different cellular behaviours. Understanding context-dependent p38α signalling provides important insights into p38α roles in physiology and pathology.
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影响因子：
10.5
作者：
Brichkina A;Bertero T;Loh HM;Nguyen NT;Emelyanov A;Rigade S;Ilie M;Hofman P;Gaggioli C;Bulavin DV
通讯作者：
Bulavin DV
DOI：
10.1002/jcsm.12354
发表时间：
2018-10
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
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作者：
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作者：
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64.5
作者：
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通讯作者：
Krogan, Nevan J.
影响因子：
10.5
作者：
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通讯作者：
Hemann MT