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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
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
{"title":"The inositol phosphate signalling network in physiology and disease","authors":"Seyun Kim ,&nbsp;Rashna Bhandari ,&nbsp;Charles A. Brearley ,&nbsp;Adolfo Saiardi","doi":"10.1016/j.tibs.2024.08.005","DOIUrl":"10.1016/j.tibs.2024.08.005","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 969-985"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them","authors":"Bocheng Wu ,&nbsp;Angela N. Koehler ,&nbsp;Peter M.K. Westcott","doi":"10.1016/j.tibs.2024.08.002","DOIUrl":"10.1016/j.tibs.2024.08.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 1014-1029"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Bridging brain insulin resistance to Alzheimer’s pathogenesis","authors":"Wenqiang Chen ,&nbsp;Valdemar Brimnes Ingemann Johansen ,&nbsp;Cristina Legido-Quigley","doi":"10.1016/j.tibs.2024.09.004","DOIUrl":"10.1016/j.tibs.2024.09.004","url":null,"abstract":"<div><div>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, <span><span>Lanzillotta <em>et al.</em></span><svg><path></path></svg></span> 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.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 939-941"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"The quest to identify ADP-ribosylation readers: methodological advances","authors":"Suzanne A. Weijers ,&nbsp;Michiel Vermeulen ,&nbsp;Katarzyna W. Kliza","doi":"10.1016/j.tibs.2024.08.006","DOIUrl":"10.1016/j.tibs.2024.08.006","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 1000-1013"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"The expanding landscape of canonical and non-canonical protein phosphorylation","authors":"Thibault Houles ,&nbsp;Sang-Oh Yoon ,&nbsp;Philippe P. Roux","doi":"10.1016/j.tibs.2024.08.004","DOIUrl":"10.1016/j.tibs.2024.08.004","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 986-999"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
Trends in Biochemical Sciences Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.06.002
Xudong Wu
{"title":"Nanobody-assisted cryoEM structural determination for challenging proteins","authors":"Xudong Wu","doi":"10.1016/j.tibs.2024.06.002","DOIUrl":"10.1016/j.tibs.2024.06.002","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 1030-1031"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
Trends in Biochemical Sciences Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.07.007
Germán Rivas , Allen P. Minton
{"title":"Surfaces as frameworks for intracellular organization","authors":"Germán Rivas ,&nbsp;Allen P. Minton","doi":"10.1016/j.tibs.2024.07.007","DOIUrl":"10.1016/j.tibs.2024.07.007","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 942-954"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
Trends in Biochemical Sciences Pub Date : 2024-11-01 DOI: 10.1016/j.tibs.2024.09.002
Yuri Shibata
{"title":"Efficient PROTAC-ing: combinational use of PROTACs with signaling pathway inhibitors","authors":"Yuri Shibata","doi":"10.1016/j.tibs.2024.09.002","DOIUrl":"10.1016/j.tibs.2024.09.002","url":null,"abstract":"<div><div>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, <span><span>Mori <em>et al.</em></span><svg><path></path></svg></span> identified certain inhibitors of cellular pathways, such as PARylation and proteostatic pathways, which enhance proteolysis-targeting chimera (PROTAC)-induced protein degradation.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 11","pages":"Pages 936-938"},"PeriodicalIF":11.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Visualizing intermediate stages of viral membrane fusion by cryo-electron tomography 通过低温电子断层扫描观察病毒膜融合的中间阶段。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.06.012
Sally M. Kephart , Nancy Hom , Kelly K. Lee
{"title":"Visualizing intermediate stages of viral membrane fusion by cryo-electron tomography","authors":"Sally M. Kephart ,&nbsp;Nancy Hom ,&nbsp;Kelly K. Lee","doi":"10.1016/j.tibs.2024.06.012","DOIUrl":"10.1016/j.tibs.2024.06.012","url":null,"abstract":"<div><div>Protein-mediated membrane fusion is the dynamic process where specialized protein machinery undergoes dramatic conformational changes that drive two membrane bilayers together, leading to lipid mixing and opening of a fusion pore between previously separate membrane-bound compartments. Membrane fusion is an essential stage of enveloped virus entry that results in viral genome delivery into host cells. Recent studies applying cryo-electron microscopy techniques in a time-resolved fashion provide unprecedented glimpses into the interaction of viral fusion proteins and membranes, revealing fusion intermediate states from the initiation of fusion to release of the viral genome. In combination with complementary structural, biophysical, and computation modeling approaches, these advances are shedding new light on the mechanics and dynamics of protein-mediated membrane fusion.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 10","pages":"Pages 916-931"},"PeriodicalIF":11.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling intracellular phase separation: advances in optical imaging of biomolecular condensates 揭示细胞内的相分离：生物分子凝聚物光学成像的进展。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.06.014
Yinfeng Guo (郭寅风) , Xin Zhang (张鑫)
{"title":"Unveiling intracellular phase separation: advances in optical imaging of biomolecular condensates","authors":"Yinfeng Guo (郭寅风) ,&nbsp;Xin Zhang (张鑫)","doi":"10.1016/j.tibs.2024.06.014","DOIUrl":"10.1016/j.tibs.2024.06.014","url":null,"abstract":"<div><div>Intracellular biomolecular condensates, which form via phase separation, display a highly organized ultrastructure and complex properties. Recent advances in optical imaging techniques, including super-resolution microscopy and innovative microscopic methods that leverage the intrinsic properties of the molecules observed, have transcended the limitations of conventional microscopies. These advances facilitate the exploration of condensates at finer scales and in greater detail. The deployment of these emerging but sophisticated imaging tools allows for precise observations of the multiphasic organization and physicochemical properties of these condensates, shedding light on their functions in cellular processes. In this review, we highlight recent progress in methodological innovations and their profound implications for understanding the organization and dynamics of intracellular biomolecular condensates.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 10","pages":"Pages 901-915"},"PeriodicalIF":11.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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