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The Integrator-PP2A complex integrates promoter-proximal premature termination with chromatin context and genome maintenance. 整合子- pp2a复合体将启动子-近端过早终止与染色质背景和基因组维持结合起来。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-10 DOI: 10.1016/j.tibs.2025.09.006
Aixia Song, Danyi Lu, Fei Xavier Chen
{"title":"The Integrator-PP2A complex integrates promoter-proximal premature termination with chromatin context and genome maintenance.","authors":"Aixia Song, Danyi Lu, Fei Xavier Chen","doi":"10.1016/j.tibs.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.09.006","url":null,"abstract":"<p><p>Well-regulated transcription is essential for maintaining cellular homeostasis and genome integrity. The Integrator-PP2A complex has emerged as a major regulator of transcription by stimulating promoter-proximal termination of RNA polymerase II (Pol II). By employing dual catalytic activities, Integrator-PP2A shapes transcriptional output, limits aberrant RNA production, and suppresses R-loop-associated genome instability. Integrator-PP2A is highly modular, enabling dynamic interactions with transcription factors and epigenetic modifiers in distinct chromatin contexts and serving as a molecular hub that links transcriptional regulation to RNA quality control, chromatin state, and genome surveillance. Here, we review recent insights into the composition, mechanisms, and regulatory functions of this complex, which together establish its broad roles across both coding and noncoding transcriptional programs.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273483","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
Zn2+ transients and signaling in mammalian systems. 哺乳动物系统中的Zn2+瞬态和信号传导。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-04 DOI: 10.1016/j.tibs.2025.09.002
Ananya Rakshit, Amy E Palmer
{"title":"Zn<sup>2+</sup> transients and signaling in mammalian systems.","authors":"Ananya Rakshit, Amy E Palmer","doi":"10.1016/j.tibs.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.09.002","url":null,"abstract":"<p><p>Labile zinc (Zn<sup>2+</sup>) represents an important fraction of the total intracellular zinc pool that is readily available for binding. The signaling function of labile Zn<sup>2+</sup> lies in its dynamic nature. Fluctuations in labile Zn<sup>2+</sup> concentrations caused by either endogenous or exogenous stimuli can transiently influence cellular microenvironments, leading to modulation of signaling pathways. In this review, we focus on recent findings of zinc transients that influence cellular processes in mammalian systems. We highlight different types of zinc transients and how cellular zinc status plays regulatory roles in early development, gene expression, and kinase or neuronal signaling. Although the molecular mechanism behind how zinc transients activate signaling cascades is not clear in all cases, charting these interactions is the first step in the process.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231191","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
Interconnectivity of mitochondrial protein biogenesis and quality control. 线粒体蛋白生物发生与质量控制的互联性。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-02 DOI: 10.1016/j.tibs.2025.09.004
Abi S Ghifari, Carmela Vazquez-Calvo, Andreas Carlström, Martin Ott
{"title":"Interconnectivity of mitochondrial protein biogenesis and quality control.","authors":"Abi S Ghifari, Carmela Vazquez-Calvo, Andreas Carlström, Martin Ott","doi":"10.1016/j.tibs.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.09.004","url":null,"abstract":"<p><p>Mitochondrial protein homeostasis (proteostasis) keeps the mitochondrial proteome functional. Thus, proteostasis is essential for mitochondrial activity and overall cellular functions, and a reduction in its function corresponds with diseases and aging in humans. Recent studies in various model organisms highlight components and mechanisms of mitochondrial proteostasis from biogenesis, through assembly, to turnover. Key findings include the identification of new components and mechanistic insights into protein import and mitochondrial translation processes, the interconnectivity of protein biogenesis and quality control, and proteolytic degradation machineries. In this review we discuss these advances that improve our current understanding of the inner workings and significance of the mitochondrial proteostasis network in maintaining functional mitochondria.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224665","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
Mitochondrial dynamics and pore formation in regulated cell death pathways. 线粒体动力学和孔形成调控细胞死亡途径。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-02 DOI: 10.1016/j.tibs.2025.09.001
Lisa Hohorst, Uris Ros, Ana J Garcia-Saez
{"title":"Mitochondrial dynamics and pore formation in regulated cell death pathways.","authors":"Lisa Hohorst, Uris Ros, Ana J Garcia-Saez","doi":"10.1016/j.tibs.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.tibs.2025.09.001","url":null,"abstract":"<p><p>Mitochondria act as central hubs for cell death signaling. During apoptosis and regulated necrosis (pyroptosis, necroptosis, and ferroptosis), mitochondria undergo drastic changes including membrane permeabilization, fragmentation, and loss of membrane potential. However, dissection of the mechanisms underlying these processes is challenging because they involve remodeling of mitochondrial membranes coupled to the assembly of protein complexes whose dynamics are difficult to capture. We discuss progress in our understanding of mitochondrial alterations in cell death and highlight state-of-the-art experimental approaches to study them. We focus on advanced single-molecule and correlative microscopy methods which have recently provided unprecedented details about the dynamics and structure of protein complexes in mitochondria and their impact on membrane organization.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224763","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
Advisory Board and Contents 咨询委员会及内容
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/S0968-0004(25)00227-0
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/S0968-0004(25)00227-0","DOIUrl":"10.1016/S0968-0004(25)00227-0","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages i-ii"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204411","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
Tissue expansion enables proteomics at improved spatial resolution 组织扩展使蛋白质组学在提高空间分辨率。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.06.002
Zhen Dong (董振) , Wenhao Jiang (姜玟昊) , Tiannan Guo (郭天南)
{"title":"Tissue expansion enables proteomics at improved spatial resolution","authors":"Zhen Dong (董振) ,&nbsp;Wenhao Jiang (姜玟昊) ,&nbsp;Tiannan Guo (郭天南)","doi":"10.1016/j.tibs.2025.06.002","DOIUrl":"10.1016/j.tibs.2025.06.002","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 945-946"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367783","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
Subscription and Copyright Information 订阅及版权资料
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/S0968-0004(25)00230-0
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/S0968-0004(25)00230-0","DOIUrl":"10.1016/S0968-0004(25)00230-0","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Page e1"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204366","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
Mitochondrial tRNA processing: a neutral evolutionary ratchet innovation 线粒体tRNA加工：中性进化棘轮创新。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.05.008
Lien B. Lai , Jane E. Jackman , Charles J. Daniels , Venkat Gopalan
{"title":"Mitochondrial tRNA processing: a neutral evolutionary ratchet innovation","authors":"Lien B. Lai ,&nbsp;Jane E. Jackman ,&nbsp;Charles J. Daniels ,&nbsp;Venkat Gopalan","doi":"10.1016/j.tibs.2025.05.008","DOIUrl":"10.1016/j.tibs.2025.05.008","url":null,"abstract":"<div><div>Mitochondrial tRNA processing is a chronicle of molecular adaptability. The processing of structurally compromised tRNAs is unexpectedly rescued by a multienzyme complex shaped by constructive neutral evolution. This striking example of biological complexity arising from nonadaptive mechanisms showcases how a potential vulnerability is transformed into a robust, if precarious, innovation.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 842-844"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525856","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
Intrinsic disorder and fuzzy interactions drive multiple functions of HMGB1 HMGB1的内在失序和模糊相互作用驱动其多种功能。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.08.001
Michela Ghitti , Liam Sean Colley , Malisa Vittoria Mantonico , Giovanna Musco , Marco Emilio Bianchi
{"title":"Intrinsic disorder and fuzzy interactions drive multiple functions of HMGB1","authors":"Michela Ghitti ,&nbsp;Liam Sean Colley ,&nbsp;Malisa Vittoria Mantonico ,&nbsp;Giovanna Musco ,&nbsp;Marco Emilio Bianchi","doi":"10.1016/j.tibs.2025.08.001","DOIUrl":"10.1016/j.tibs.2025.08.001","url":null,"abstract":"<div><div>HMGB1, a multitasking protein, is scrutinized here through the lens of the 'fuzzy interactions' driven by its intrinsically disordered regions (IDRs). Although the multiple intracellular and extracellular functions of this protein have been studied for decades, viewing HMGB1 as fuzzy and dynamic provides a novel perspective. Recent breakthroughs emphasize the crucial role of its IDRs, especially the acidic C-terminal tail, in mediating dynamic multivalent interactions. This fuzziness enables HMGB1 to modulate DNA and chromatin binding, to chaperone other proteins such as p53, and to tune inflammatory signals via receptors such as TLR4 and CXCR4. Understanding the fuzzy nature of HMGB1 unlocks new therapeutic strategies targeting both its structured and unstructured regions to tackle a range of diseases.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 906-918"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938131","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
Engineered protein inhibitors for precise targeting of matrix metalloproteinases 精确靶向基质金属蛋白酶的工程蛋白抑制剂。
IF 11 1区 生物学
Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI: 10.1016/j.tibs.2025.08.002
Naama Rotenberg , Noam Y. Bentolila , Julia M. Shifman
{"title":"Engineered protein inhibitors for precise targeting of matrix metalloproteinases","authors":"Naama Rotenberg ,&nbsp;Noam Y. Bentolila ,&nbsp;Julia M. Shifman","doi":"10.1016/j.tibs.2025.08.002","DOIUrl":"10.1016/j.tibs.2025.08.002","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs) are a family of 23 zinc-dependent proteases involved in extracellular matrix (ECM) remodeling and are implicated in diseases such as cancer, arthritis, and cardiovascular disorders. Broad-spectrum MMP inhibitors (MMPIs) have proven counterproductive due to the protective roles of certain MMPs and their expression in healthy tissues. Recent advances in protein engineering have enabled the development of highly specific protein-based MMPIs that precisely target individual MMPs. These engineered proteins, often derived from antibody fragments or endogenous MMPIs, offer enhanced selectivity, reduced off-target effects, and improved therapeutic efficacy. This review highlights novel strategies for the precise targeting of MMPs using engineered proteins and discusses their potential to transform diagnostics and treatment of MMP-driven diseases.</div></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"50 10","pages":"Pages 919-930"},"PeriodicalIF":11.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038867","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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