The dynamic and stress-adaptive signaling hub of 14-3-3: emerging mechanisms of regulation and context-dependent protein-protein interactions.
The dynamic and stress-adaptive signaling hub of 14-3-3: emerging mechanisms of regulation and context-dependent protein-protein interactions.
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DOI：
10.1038/s41388-018-0348-3
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发表时间：
2018-10
期刊：
影响因子：
8
通讯作者：
Andersen JL
中科院分区：
文献类型：
--
作者：
Pennington KL;Chan TY;Torres MP;Andersen JL
14-3-3 蛋白是一个结构相似的磷酸结合蛋白家族，基本上调节所有主要的细胞功能。数十年对 14-3-3 的研究揭示了一个非凡的相互作用蛋白质网络，展示了 14-3-3 如何整合和控制多个信号通路。特别是，这些相互作用将 14-3-3 置于控制癌症关键过程的信号中枢的中心，包括细胞凋亡、细胞周期进程、自噬、葡萄糖代谢和细胞运动。历史上，大多数 14-3-3 相互作用都是在营养充足的细胞培养条件下鉴定和研究的，这揭示了重要的营养驱动的相互作用。然而，这低估了 14-3-3 的影响范围。事实上，营养物质、生长因子的损失或其他环境条件的变化（例如基因毒性应激）不仅会导致14-3-3相互作用稳态的丧失，还会引发新的相互作用，其中许多可能是应激适应性的。 14-3-3 相互作用组的这种动态性质开始成为人们关注的焦点，因为质谱技术的进步有助于更深入地探索和识别环境依赖性的 14-3-3 相互作用，为了解适应性磷酸化驱动的细胞机制提供了一个窗口，这些机制协调肿瘤细胞对各种环境条件（包括缺氧和化疗）的反应。在这篇综述中，我们讨论了新兴的 14-3-3 调控机制，重点关注 14-3-3 的翻译后调控和动态蛋白质-蛋白质相互作用，说明 14-3-3 作为癌症中压力适应性信号中枢的作用。
14-3-3 proteins are a family of structurally similar phospho-binding proteins that regulate essentially every major cellular function. Decades of research on 14-3-3s have revealed a remarkable network of interacting proteins that demonstrate how 14-3-3s integrate and control multiple signaling pathways. In particular, these interactions place 14-3-3 at the center of the signaling hub that governs critical processes in cancer, including apoptosis, cell cycle progression, autophagy, glucose metabolism, and cell motility. Historically, the majority of 14-3-3 interactions have been identified and studied under nutrient-replete cell culture conditions, which has revealed important nutrient driven interactions. However, this underestimates the reach of 14-3-3s. Indeed, the loss of nutrients, growth factors, or changes in other environmental conditions (e.g., genotoxic stress) will not only lead to the loss of homeostatic 14-3-3 interactions, but also trigger new interactions, many of which are likely stress adaptive. This dynamic nature of the 14-3-3 interactome is beginning to come into focus as advancements in mass spectrometry are helping to probe deeper and identify context-dependent 14-3-3 interactions—providing a window into adaptive phosphorylation-driven cellular mechanisms that orchestrate the tumor cell’s response to a variety of environmental conditions including hypoxia and chemotherapy. In this review, we discuss emerging 14-3-3 regulatory mechanisms with a focus on post-translational regulation of 14-3-3 and dynamic protein–protein interactions that illustrate 14-3-3’s role as a stress-adaptive signaling hub in cancer.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
DOI：
10.1073/pnas.96.7.3745
发表时间：
1999-03-30
影响因子：
11.1
作者：
Brown, AL;Lee, CH;Chung, JH
通讯作者：
Chung, JH
影响因子：
7.2
作者：
Cao, Weidong;Yang, Xiaoliang;Fei, Zhou
通讯作者：
Fei, Zhou
影响因子：
3.8
作者：
Cheruiyot A;Paudyal SC;Kim IK;Sparks M;Ellenberger T;Piwnica-Worms H;You Z
通讯作者：
You Z
影响因子：
3.3
作者：
Acevedo, Summer F.;Tsigkari, K. Kirki;Skoulakis, Efthimios M. C.
通讯作者：
Skoulakis, Efthimios M. C.