A guide to ERK dynamics, part 2: downstream decoding.

A guide to ERK dynamics, part 2: downstream decoding.
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ERK动力学指南,第2部分:下游解码。

DOI:
10.1042/bcj20230277
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发表时间:
2023-12-13
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
--
中科院分区:
其他
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--
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细胞外信号调节激酶(ERK)途径的信号传导控制许多细胞过程,包括细胞分裂、死亡和分化。在这两部分审查的第二部分中,我们解决了ERK通路如何对多个过程产生独特和特定背景的影响的问题。我们讨论了ERK活性的动态如何诱导基因表达程序的选择性变化,从实验和计算模型的见解。重点是基于单细胞生物传感器的研究,我们总结了ERK信号在组织中的四种主要功能模式:调节细胞群体的大小,基于梯度的模式,形态变化的波传播,以及细胞基因表达状态的多样化。这些运作模式在癌症和其他相关疾病中被破坏,并代表治疗干预的潜在靶点。通过了解ERK信号转导的动态机制,不仅可以简单地抑制ERK,而且可以恢复功能活动模式并改善疾病结局的药理学策略。
Signaling by the extracellular signal-regulated kinase (ERK) pathway controls many cellular processes, including cell division, death, and differentiation. In this second installment of a two-part review, we address the question of how the ERK pathway exerts distinct and context-specific effects on multiple processes. We discuss how the dynamics of ERK activity induce selective changes in gene expression programs, with insights from both experiments and computational models. With a focus on single-cell biosensor-based studies, we summarize four major functional modes for ERK signaling in tissues: adjusting the size of cell populations, gradient-based patterning, wave propagation of morphological changes, and diversification of cellular gene expression states. These modes of operation are disrupted in cancer and other related diseases and represent potential targets for therapeutic intervention. By understanding the dynamic mechanisms involved in ERK signaling, there is potential for pharmacological strategies that not only simply inhibit ERK, but also restore functional activity patterns and improve disease outcomes.
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