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Programmable protein editing 可编程的蛋白质编辑。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.06.008
Carly K. Schissel
{"title":"Programmable protein editing","authors":"Carly K. Schissel","doi":"10.1016/j.tibs.2025.06.008","DOIUrl":"10.1016/j.tibs.2025.06.008","url":null,"abstract":"<div><div>Installation of unnatural chemical motifs and structures into proteins in living cells is challenging. Recent work by <span><span>Beyer <em>et al</em></span><svg><path></path></svg></span><em>.</em><span><span> demonstrated programmable protein editing by installing two split intein<span> pairs into a protein of interest, which splice in a fully synthetic peptide sequence inside </span></span>mammalian cells.</span></div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 837-838"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525857","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
LRRC8/VRAC chloride and metabolite channels in signaling and volume regulation LRRC8/VRAC氯离子和代谢物通道在信号和体积调节中的作用。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.07.001
Fabian M.B. Thöne , Maya M. Polovitskaya , Thomas J. Jentsch
{"title":"LRRC8/VRAC chloride and metabolite channels in signaling and volume regulation","authors":"Fabian M.B. Thöne ,&nbsp;Maya M. Polovitskaya ,&nbsp;Thomas J. Jentsch","doi":"10.1016/j.tibs.2025.07.001","DOIUrl":"10.1016/j.tibs.2025.07.001","url":null,"abstract":"<div><div>Volume-regulated anion channels (VRACs) are almost ubiquitously expressed plasma membrane (PM) channels of vertebrate cells with roles in cell volume regulation and signaling. Besides conducting anions such as chloride, VRACs transport metabolites, neurotransmitters, immunomodulators, and drugs irrespective of their electrical charge. VRAC-mediated transport of these molecules has profound (patho)physiological significance. The recent identification of VRACs as heteromers of up to five different LRRC8 proteins allowed the roles of VRACs to be addressed with genetic and molecular tools. Cryogenic electron microscopy (cryo-EM) and mutagenesis yielded insights into the structure and function of VRACs, yet their activation mechanisms remain enigmatic. Here we focus on new developments and suggest that the ability of VRAC to transport metabolites and signaling molecules may be physiologically more important than its role in cell volume regulation.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 873-891"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793181","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
PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease PTMs作为分子编码器：在疾病网络控制中将伴侣重编程为表表观体。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.07.006
Feixia Chu , Sahil Sharma , Stephen D. Ginsberg , Gabriela Chiosis
{"title":"PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease","authors":"Feixia Chu ,&nbsp;Sahil Sharma ,&nbsp;Stephen D. Ginsberg ,&nbsp;Gabriela Chiosis","doi":"10.1016/j.tibs.2025.07.006","DOIUrl":"10.1016/j.tibs.2025.07.006","url":null,"abstract":"<div><div>Recent discoveries reveal that post-translational modifications (PTMs) do more than regulate protein activity – they encode conformational states that transform chaperones into epichaperomes: multimeric scaffolds that rewire protein–protein interaction networks. This emerging paradigm expands the framework of chaperone biology in disease and provides a structural basis for systems-level dysfunction in disorders such as cancer and Alzheimer’s disease. This review explores how PTMs within intrinsically disordered regions drive epichaperome formation, how these scaffolds selectively regulate disease-enabling functions, and why their disruption normalizes pathological networks. By highlighting PTMs as molecular encoders of supramolecular assemblies, we propose a shift from targeting proteins to targeting network architectures that sustain and perpetuate disease – a concept with broad implications for cell biology, disease propagation, and therapeutic design.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 892-905"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938276","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
Exploring nondegrading molecular glues for protein–protein interactions 探索蛋白质相互作用的非降解分子胶。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.07.005
Sitong Yu , Lixin Zhou , Jing Yang , Jian Zhang , Wenchao Lu
{"title":"Exploring nondegrading molecular glues for protein–protein interactions","authors":"Sitong Yu ,&nbsp;Lixin Zhou ,&nbsp;Jing Yang ,&nbsp;Jian Zhang ,&nbsp;Wenchao Lu","doi":"10.1016/j.tibs.2025.07.005","DOIUrl":"10.1016/j.tibs.2025.07.005","url":null,"abstract":"<div><div>Protein–protein interactions (PPIs) are central to cellular signaling and represent attractive, yet challenging drug targets. While molecular glue degraders (MGDs) promote target degradation via E3 ligase recruitment, nondegrading molecular glues (MGs) act independently of ubiquitination to stabilize PPIs, enabling modulation of complex assembly, localization, and signaling. In this review, we outline recent progress in nondegrading MGs, highlighting key presenter proteins, such as FKBP12, Cyclophilin A, and 14-3-3, along with emerging case studies beyond these canonical systems. Advances in chemical biology, structural analysis, and computational design are accelerating discovery in this emerging field. Collectively, these insights position nondegrading MGs as a promising therapeutic modality with distinct mechanisms and broad translational potential.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 845-872"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938179","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
Conserved signaling gears that sustain circadian clock robustness 维持生物钟稳健性的保守信号装置。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.06.013
Felipe Muñoz-Guzmán , Luis F. Larrondo
{"title":"Conserved signaling gears that sustain circadian clock robustness","authors":"Felipe Muñoz-Guzmán ,&nbsp;Luis F. Larrondo","doi":"10.1016/j.tibs.2025.06.013","DOIUrl":"10.1016/j.tibs.2025.06.013","url":null,"abstract":"<div><div>Circadian clocks maintain the correct period despite nutritional fluctuations, a property known as metabolic compensation (MC). In a recent report, <span><span>Sárkány <em>et al.</em></span><svg><path></path></svg></span><span> reveal a conserved role for Ras guanine nucleotide exchange factor (RasGEF) signaling in MC from fungi to human cells. Their findings highlight how this pathway buffers circadian function under glucose deprivation, integrating metabolic cues into clock dynamic robustness.</span></div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 839-841"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615698","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
How interactions between oxidized DNA and the NLRP3 inflammasome fuel inflammatory disease 氧化DNA和NLRP3炎性体之间的相互作用如何促进炎症性疾病。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.07.007
Angela Lackner , Lemuel Leonidas , Alijah Macapagal , Hannah Lee , Reginald McNulty
{"title":"How interactions between oxidized DNA and the NLRP3 inflammasome fuel inflammatory disease","authors":"Angela Lackner ,&nbsp;Lemuel Leonidas ,&nbsp;Alijah Macapagal ,&nbsp;Hannah Lee ,&nbsp;Reginald McNulty","doi":"10.1016/j.tibs.2025.07.007","DOIUrl":"10.1016/j.tibs.2025.07.007","url":null,"abstract":"<div><div>Recent discoveries have emphasized the critical role of oxidized DNA (ox-DNA) in inflammation and immune regulation. Produced during oxidative stress from infection or tissue damage, ox-DNA activates signaling pathways that drive the release of proinflammatory cytokines, specifically engaging the NLRP3 inflammasome, a key player in cytokine maturation and host defense. NLRP3 is increasingly implicated in inflammatory and autoimmune diseases, with ox-DNA recognized as a central activator of this inflammasome. This review examines the role of ox-DNA in inflammasome activation, its broader impact on inflammatory processes, and promising therapeutic approaches targeting ox-DNA through both immunological and structural lenses. These insights highlight ox-DNA’s relevance in inflammation and offer potential avenues for the treatment of a range of immune-related disorders.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 931-944"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938112","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
Daily standup meeting: enhancing accountability and psychological safety. 每日站立会议：强化问责和心理安全感。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-09-30 DOI: 10.1016/j.tibs.2025.08.009
Stefania Tocci, Aspen L Hirsch, Jessica W Tsai
{"title":"Daily standup meeting: enhancing accountability and psychological safety.","authors":"Stefania Tocci, Aspen L Hirsch, Jessica W Tsai","doi":"10.1016/j.tibs.2025.08.009","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.08.009","url":null,"abstract":"<p><p>Research laboratories often struggle to maintain a trusting environment which negatively affects team cohesion. Daily standup meetings provide a means to enhance communication, transparency, and psychological safety. In this article, we highlight the potential benefits of integrating daily standup meetings into your laboratory routine to promote accountability and teamwork.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205261","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 nuclear export receptor CRM1/XPO1 and its diverse cargoes. 核出口受体CRM1/XPO1及其各种货物。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-09-27 DOI: 10.1016/j.tibs.2025.09.003
Ralph H Kehlenbach, Yuh Min Chook
{"title":"The nuclear export receptor CRM1/XPO1 and its diverse cargoes.","authors":"Ralph H Kehlenbach, Yuh Min Chook","doi":"10.1016/j.tibs.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.09.003","url":null,"abstract":"<p><p>CRM1 (Exportin 1, XPO1), the best-characterized nuclear export receptor, exports hundreds of proteins and various RNA species. Its broad cargo repertoire necessitates versatile binding modes for diverse interaction partners, including nuclear export signal/sequence (NES)-containing cargoes, the GTPase Ran, nucleoporins that line nuclear pore complexes, and accessory proteins that facilitate export complex assembly or disassembly. We review the current knowledge of CRM1's protein and RNA cargoes and examine its modes of interactions in the context of the basic mechanism of nuclear export - NES recognition, recent structural studies that reveal how CRM1 engages cargoes beyond NESs, and allosteric regulation. Finally, we touch on the state of NES/cargo prediction, CRM1's interactions with nucleoporins, and its emerging roles beyond nuclear export.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184493","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 interplay of the cGAS-STING pathway with the lysosome. cGAS-STING途径与溶酶体的相互作用。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-09-23 DOI: 10.1016/j.tibs.2025.08.010
Yinfeng Xu, Wei Wan
{"title":"The interplay of the cGAS-STING pathway with the lysosome.","authors":"Yinfeng Xu, Wei Wan","doi":"10.1016/j.tibs.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.08.010","url":null,"abstract":"<p><p>The cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon (IFN) genes (STING) pathway detects cytoplasmic DNA and elicits the innate immune response. Several recent studies show that cGAS-STING signaling not only terminates at the lysosome but also regulates lysosomal function. Here, we discuss the interplay of the cGAS-STING pathway with the lysosome.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136057","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
Mapping rRNA, tRNA, and mRNA modifications in ribosomes at high resolution. 高分辨率绘制核糖体中的rRNA、tRNA和mRNA修饰。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-09-16 DOI: 10.1016/j.tibs.2025.08.007
Łukasz Koziej, Sebastian Glatt
{"title":"Mapping rRNA, tRNA, and mRNA modifications in ribosomes at high resolution.","authors":"Łukasz Koziej, Sebastian Glatt","doi":"10.1016/j.tibs.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.08.007","url":null,"abstract":"<p><p>Chemical modifications of rRNA, tRNA, and mRNA play key roles in protein synthesis by affecting the structure of these RNAs, by modulating decoding, and by influencing ribosomal efficiency. Recent advances in sequencing-based detection methods have expanded our ability to map these moieties across RNA molecules in diverse cellular states. In parallel, X-ray crystallography and the advent of high-resolution cryogenic electron microscopy have facilitated the direct visualization of RNA modifications within ribosomes. This review integrates recent structural studies with functional insights to shed light on the roles of RNA modifications in translation. Thereby, we seek to summarize current knowledge about the molecular roles of RNA modifications in gene expression and protein synthesis.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079207","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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