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Advisory Board and Contents 咨询委员会和内容
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/S0968-0004(24)00238-X
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引用次数: 0
The inositol phosphate signalling network in physiology and disease 生理和疾病中的磷酸肌醇信号网络。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.08.005
Seyun Kim , Rashna Bhandari , Charles A. Brearley , Adolfo Saiardi
Combinatorial substitution of phosphate groups on the inositol ring gives rise to a plethora of inositol phosphates (InsPs) and inositol pyrophosphates (PP-InsPs). These small molecules constitute an elaborate metabolic and signalling network that influences nearly every cellular function. This review delves into the knowledge accumulated over the past decades regarding the biochemical principles and significance of InsP metabolism. We focus on the biological actions of InsPs in mammals, with an emphasis on recent findings regarding specific target proteins. We further discuss the roles of InsP metabolism in contributing to physiological homeostasis and pathological conditions. A deeper understanding of InsPs and their metabolic pathways holds the potential to address unresolved questions and propel advances towards therapeutic applications.
肌醇环上磷酸基团的组合取代产生了大量肌醇磷酸盐（InsPs）和肌醇焦磷酸盐（PP-InsPs）。这些小分子构成了一个复杂的代谢和信号网络，影响着几乎所有的细胞功能。本综述深入探讨了过去几十年中积累的有关 InsP 代谢的生化原理和意义的知识。我们重点探讨了 InsPs 在哺乳动物体内的生物作用，并着重介绍了有关特定靶蛋白的最新发现。我们进一步讨论了 InsP 代谢在生理平衡和病理状态中的作用。加深对 InsPs 及其代谢途径的了解有可能解决悬而未决的问题，并推动治疗应用的进展。
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引用次数: 0
New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them 克服 T 细胞功能障碍的新机遇：转录因子的作用及其靶向方法。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.08.002
Bocheng Wu , Angela N. Koehler , Peter M.K. Westcott
Immune checkpoint blockade (ICB) therapies, which block inhibitory receptors on T cells, can be efficacious in reinvigorating dysfunctional T cell responses. However, most cancers do not respond to these therapies and even in those that respond, tumors can acquire resistance. New strategies are needed to rescue and recruit T cell responses across patient populations and disease states. In this review, we define mechanisms of T cell dysfunction, focusing on key transcription factor (TF) networks. We discuss the complex and sometimes contradictory roles of core TFs in both T cell function and dysfunction. Finally, we review strategies to target TFs using small molecule modulators, which represent a challenging but highly promising opportunity to tune the T cell response toward sustained immunity.
免疫检查点阻断（ICB）疗法可阻断T细胞上的抑制性受体，从而有效重振功能失调的T细胞反应。然而，大多数癌症对这些疗法没有反应，即使有反应的肿瘤也会产生抗药性。我们需要新的策略来挽救和招募不同患者群体和疾病状态下的 T 细胞应答。在这篇综述中，我们定义了 T 细胞功能障碍的机制，重点关注关键转录因子 (TF) 网络。我们讨论了核心 TF 在 T 细胞功能和功能障碍中复杂且有时相互矛盾的作用。最后，我们回顾了使用小分子调节剂靶向 TFs 的策略，这是调整 T 细胞反应以实现持续免疫的一个极具挑战性但又大有希望的机会。
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引用次数: 0
Bridging brain insulin resistance to Alzheimer’s pathogenesis 将大脑胰岛素抵抗与阿尔茨海默氏症发病机制联系起来。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.09.004
Wenqiang Chen , Valdemar Brimnes Ingemann Johansen , Cristina Legido-Quigley
Emerging evidence links type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD), with brain insulin resistance (BIR) as a key factor. In a recent study, Lanzillotta et al. reveal that reduced biliverdin reductase-A (BVR-A) impairs glycogen synthase kinase 3β (GSK3β) phosphorylation, causing mitochondrial dysfunction and exacerbating brain insulin resistance in the progression of both T2DM and AD.
越来越多的证据表明，2 型糖尿病（T2DM）和阿尔茨海默病（AD）之间存在联系，而脑胰岛素抵抗（BIR）是其中的一个关键因素。在最近的一项研究中，Lanzillotta 等人发现，胆绿素还原酶-A（BVR-A）的减少会损害糖原合成酶激酶 3β （GSK3β）的磷酸化，导致线粒体功能障碍，并在 T2DM 和 AD 的进展过程中加剧脑胰岛素抵抗。
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引用次数: 0
The quest to identify ADP-ribosylation readers: methodological advances 鉴别 ADP 核糖基化阅读器的探索：方法学上的进步。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.08.006
Suzanne A. Weijers , Michiel Vermeulen , Katarzyna W. Kliza
ADP-ribosylation regulates numerous fundamental cellular processes in health and disease. However, the limited availability of suitable tools and methods prevents the identification and characterization of certain components of the ADP-ribosylation signaling network and, consequently, efficient utilization of their biomedical potential. Identification of ADP-ribose (ADPr) readers has been particularly impeded by challenges associated with the development of ADPr-based enrichment probes. These difficulties were finally overcome in several recent studies describing various approaches to identifying ADPr readers in an unbiased, proteome-wide manner. In this review we discuss these different strategies and their limitations, benefits and drawbacks, and summarize how these technologies contribute to a dissection of ADP-ribosylation signaling networks. We also address unmet technological needs and future directions to investigate interactions with ADPr linkages.
ADP-ribosylation 调节着健康和疾病中的许多基本细胞过程。然而，由于可用的合适工具和方法有限，ADP-核糖基化信号网络中某些成分的鉴定和表征工作受到阻碍，从而无法有效利用其生物医学潜力。ADP-核糖（ADPr）阅读器的鉴定尤其受到与开发基于 ADPr 的富集探针相关的挑战的阻碍。最近的几项研究最终克服了这些困难，这些研究描述了以无偏见、全蛋白质组的方式鉴定 ADPr 阅读器的各种方法。在这篇综述中，我们讨论了这些不同的策略及其局限性、优点和缺点，并总结了这些技术如何有助于剖析 ADP-ribosylation 信号网络。我们还讨论了尚未满足的技术需求以及研究 ADPr 连接相互作用的未来方向。
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引用次数: 0
The expanding landscape of canonical and non-canonical protein phosphorylation 规范和非规范蛋白质磷酸化的不断扩展。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.08.004
Thibault Houles , Sang-Oh Yoon , Philippe P. Roux
Protein phosphorylation is a crucial regulatory mechanism in cell signaling, acting as a molecular switch that modulates protein function. Catalyzed by protein kinases and reversed by phosphoprotein phosphatases, it is essential in both normal physiological and pathological states. Recent advances have uncovered a vast and intricate landscape of protein phosphorylation that include histidine phosphorylation and more unconventional events, such as pyrophosphorylation and polyphosphorylation. Many questions remain about the true size of the phosphoproteome and, more importantly, its site-specific functional relevance. The involvement of unconventional actors such as pseudokinases and pseudophosphatases adds further complexity to be resolved. This review explores recent discoveries and ongoing challenges, highlighting the need for continued research to fully elucidate the roles and regulation of protein phosphorylation.
蛋白质磷酸化是细胞信号传导过程中的重要调节机制，是调节蛋白质功能的分子开关。它由蛋白激酶催化，由磷蛋白磷酸酶逆转，在正常生理和病理状态下都至关重要。最近的研究进展揭示了蛋白质磷酸化错综复杂的巨大格局，其中包括组氨酸磷酸化和更多非常规事件，如焦磷酸化和多磷酸化。关于磷酸化蛋白质组的真正规模，更重要的是其特定位点的功能相关性，仍存在许多问题。假激酶和假磷酸酶等非常规参与者的参与进一步增加了有待解决的复杂性。这篇综述探讨了最近的发现和正在面临的挑战，强调了继续研究以全面阐明蛋白质磷酸化的作用和调控的必要性。
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引用次数: 0
Nanobody-assisted cryoEM structural determination for challenging proteins 纳米体辅助低温电子显微镜结构测定具有挑战性的蛋白质。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.06.002
Xudong Wu
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引用次数: 0
Surfaces as frameworks for intracellular organization 作为细胞内组织框架的表面。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.07.007
Germán Rivas , Allen P. Minton
A large fraction of soluble protein within the interior of living cells may reversibly associate with structural elements, including proteinaceous fibers and phospholipid membranes. In this opinion, we present theoretical and experimental evidence that many of these associations are due to nonspecific attraction between the protein and the surface of the fiber or membrane, and that such associations may lead to substantial changes in the association state of the adsorbed proteins, the biological function of the adsorbed proteins, and the distribution of these proteins between the many microenvironments existing within the cell.
活细胞内部的大部分可溶性蛋白质可能会与结构元素（包括蛋白纤维和磷脂膜）发生可逆性结合。在本文中，我们提出了理论和实验证据，证明其中许多结合是由于蛋白质与纤维或膜表面之间的非特异性吸引力造成的，这种结合可能会导致吸附蛋白质的结合状态、吸附蛋白质的生物功能以及这些蛋白质在细胞内存在的许多微环境之间的分布发生重大变化。
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引用次数: 0
Efficient PROTAC-ing: combinational use of PROTACs with signaling pathway inhibitors 高效 PROTAC-ing：将 PROTAC 与信号通路抑制剂结合使用。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.09.002
Yuri Shibata
Targeted protein degradation is an innovative therapeutic modality for the degradation of disease-causing proteins. In a recent report combining high-throughput screening of small-molecule compounds and biochemical analyses, Mori et al. identified certain inhibitors of cellular pathways, such as PARylation and proteostatic pathways, which enhance proteolysis-targeting chimera (PROTAC)-induced protein degradation.
靶向蛋白质降解是降解致病蛋白质的一种创新疗法。最近，Mori 等人结合小分子化合物的高通量筛选和生化分析，发现了某些细胞通路（如 PARylation 和蛋白静态通路）的抑制剂，这些抑制剂能增强蛋白水解靶向嵌合体（PROTAC）诱导的蛋白质降解。
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引用次数: 0
Surviving the heat: the role of macromolecular assemblies in promoting cellular shutdown. 高温下的生存：大分子组装在促进细胞关闭中的作用。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trends in Biochemical Sciences
Pub Date : 2024-10-28 DOI: 10.1016/j.tibs.2024.09.008
Christine Desroches Altamirano, Simon Alberti

During heat shock (HS), cells orchestrate a gene expression program that promotes the synthesis of HS proteins (HSPs) while simultaneously repressing the synthesis of other proteins, including growth-promoting housekeeping proteins. Recent studies show that mRNAs encoding housekeeping proteins, along with associated processing factors, form macromolecular assemblies during HS. These assemblies inhibit transcription, nuclear export, and translation of housekeeping mRNAs, and coincide with structural rearrangements in proteins. These findings reveal a mechanism linking temperature sensitivity through structural rearrangements and macromolecular assembly to the 'shut down' of housekeeping protein synthesis. This review delves into recent findings in yeast, with a focus on macromolecular assembly, offering perspectives into mechanisms that regulate gene expression during HS and how these processes may be conserved.

在热休克（HS）过程中，细胞会协调基因表达程序，促进热休克蛋白（HSPs）的合成，同时抑制其他蛋白（包括促进生长的管家蛋白）的合成。最近的研究表明，在 HS 过程中，编码管家蛋白的 mRNA 与相关的处理因子一起形成了大分子集合体。这些集合体抑制了看门 mRNA 的转录、核输出和翻译，并与蛋白质的结构重排相吻合。这些发现揭示了通过结构重排和大分子组装将温度敏感性与 "关闭 "看门蛋白质合成联系起来的机制。这篇综述深入探讨了酵母的最新发现，重点关注大分子组装，提供了在恒温恒湿过程中调控基因表达的机制以及这些过程如何可能是保守的视角。
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