A special issue on TGF-β signaling: regulation, crosstalk, and biology
A special issue on TGF-β signaling: regulation, crosstalk, and biology
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关于 TGF-β 信号传导的特刊：调节、串扰和生物学。
DOI：
10.1093/abbs/gmx134
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Long Zhan
中科院分区：
文献类型：
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作者：
Xiaohua Yan;Long Zhan
转化生长因子β（TGF-β）是TGF-β细胞因子家族的创始成员，该家族包括TGF-βs、激活素、Nodal、骨形态发生蛋白（BMP）、生长和分化因子（GDFs）等[1-4]。所有TGF-β样成员都具有相似的信号转导模式，即与两种类型的跨膜受体结合的配体通过细胞内Smad蛋白传递其信号，然后Smad蛋白作为转录因子调节细胞核中的基因表达。此外，非Smad通路也以细胞类型和环境依赖性方式参与TGF-β诱导的生物学[5]。已经认识到，哺乳动物中几乎每种细胞类型都含有至少一种功能性TGF-β系统，因此其在胚胎发育和成体组织稳态期间参与广泛的功能。这解释了为什么TGF-β家族信号传导的扰动与广泛的疾病有关[6-9]。TGF-β本身在20世纪80年代早期被鉴定，并且在20世纪90年代中期通过TGF-β受体和Smad蛋白的功能鉴定阐明了经典的TGF-β信号传导途径。此后的20年时间里，TGF-β生物学的各个方面都取得了快速进展，包括信号转导机制、信号调节和串扰以及不同背景下的病理生理功能。本特刊介绍了12篇综述文章，以及随后几期的其他文章，尽管这些文章都在本特刊的范围内，但涵盖了我们目前对TGF-β信号传导的主要问题和最新进展的理解。为了实现其多方面和依赖于环境的功能，看似简单和直接的TGF-β/Smad途径受到在该途径的每个步骤上操作的密集和微妙的控制机制的影响。在这方面，Carl-Henrik Heldin及其同事[10]对TGF-β受体的内吞和细胞内运输途径提供了有见地的观点，这是理解受体调控的一个关键方面。Joachim Nickel和Peter ten Dijke [11]讨论了辅助受体在TGF-β家族信号传导中的重要性，并强调了结构决定因素的进展。Ye-Guang Chen和Xiaohua Yan [12]总结了许多在TGF-β信号传导中起作用的调节反馈回路，正反馈回路和负反馈回路以及涉及蛋白质调节剂和miRNA的回路。Xiaohong Fang及其同事[13]介绍了他们在活细胞中使用单分子显微镜来解析和理解TGF-β信号传导中的蛋白质-蛋白质相互作用以及所涉及的受体内吞和分选途径的最新进展。在下一个复杂性水平，TGF-β信号通过与其他途径的串扰连接并整合到细胞信号网络中。Keiji Miyazawa及其同事[14]综述了Smad 3如何与STAT 3（STAT家族的信号分子，对炎症刺激和生长因子激活的受体酪氨酸激酶有反应）交叉，以启动肿瘤发生，EMT，纤维化或免疫细胞分化中的上下文依赖性转录程序。Qiangan Xi [15]关注TGF-β/Smad信号传导与表观遗传机制之间的相互作用，包括染色质写入器，读取器和擦除器，以及作为新型表观遗传修饰剂出现的长非编码RNA。这种串扰在许多病理生理学情况下，如胚胎发育紊乱和癌症进展中具有关键重要性。TGF-β是一种多效性细胞因子，在胚胎发育和癌症进展中起关键作用。
Transforming growth factor beta (TGF-β) is the founding member of the TGF-β cytokine family, which comprises TGF-βs, Activin, Nodal, bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and others [1–4]. All the TGF-β-like members share similar signal transduction modes in that ligands binding to two types of transmembrane receptors transmit their signals via intracellular Smad proteins, which then act as transcription factors to regulate gene expression in the nucleus. In addition, non-Smad pathways are also involved in TGF-β-elicited biology in a cell typeand context-dependent manner [5]. It has been recognized that almost every cell type in mammals contains at least one functional TGF-β system, which is therefore involved in a broad range of functions during both embryonic development and adult tissue homeostasis. This explains why perturbation in TGF-β family signaling has been linked to a broad spectrum of diseases [6–9]. TGF-β itself was identified in the early 1980s and the canonical TGF-β signaling pathway was elucidated by the functional identification of TGF-β receptors and Smad proteins in the mid 1990s. Since then, a time period of 20 years has elapsed, and a rapid progress has been made in every aspect of TGF-β biology, including signal transduction mechanisms, signaling regulation and crosstalk, and pathophysiological functions in different contexts. This special issue of Acta Biochimica et Biophysica Sinica presents 12 review articles, in addition to several others in the subsequent issues albeit within the scope of this special issue, covering our current understanding of major issues of and recent advances in TGF-β signaling. In order to fulfill its multi-faceted and context-dependent functions, the seemingly simple and straight-forward TGF-β/Smad pathway is subject to intensive and delicate control mechanisms that are operating on each step of the pathway. With this regard, Carl-Henrik Heldin and colleagues [10] provide an insightful perspective on endocytic and intracellular trafficking routes of TGF-β receptors, a critical aspect for understanding receptor regulation. Joachim Nickel and Peter ten Dijke [11] discuss the emerging importance of co-receptors in TGF-β family signaling and highlight the advances in structural determinants. Ye-Guang Chen and Xiaohua Yan [12] summarize the many regulatory feedback circuits operating over TGF-β signaling, the positive and negative feedback loops as well as the circuits involving protein regulators and miRNAs. Xiaohong Fang and colleagues [13] present their recent advances on the use of single-molecule microscopy in living cells to resolve and understand the protein-protein interactions in TGF-β signaling and the receptor endocytic and sorting pathways involved. At the next level of complexity, TGF-β signaling is wired and integrated into the cellular signaling networks via crosstalk with other pathways. Keiji Miyazawa and colleagues [14] review how Smad3 intersects with STAT3, a signaling molecule of the STAT family that responds to inflammatory stimuli and growth factor-activated receptor tyrosine kinases, to initiate context-dependent transcription programs in tumorigenesis, EMT, fibrosis or immune cell differentiation. Qiaoran Xi [15] focuses on the interplay between TGF-β/Smad signaling and the epigenetic machinery, including the chromatin writers, readers and erasers, in addition to the long non-coding RNAs that are emerging as novel epigenetic modifiers. This crosstalk is of pivotal importance in many pathophysiological circumstances like disturbed embryonic development and cancer progression.TGF-β is a pleiotropic cytokine that plays a critical …