Science Signaling最新文献_第3页

Redox regulation of the transcription factor HAT1 limits basal defenses and promotes responses to infection in Arabidopsis thaliana 转录因子HAT1的氧化还原调节限制了基础防御并促进了拟南芥对感染的反应。

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-03-17 DOI: 10.1126/scisignal.aea8478

Yuqing Zhao, Fan Wei, Jiahong Lao, Peiyi Zhang, Tianyue Zhao, Dongbei Guo, Qing Han, Honghui Lin, Dawei Zhang

{"title":"Redox regulation of the transcription factor HAT1 limits basal defenses and promotes responses to infection in Arabidopsis thaliana","authors":"Yuqing Zhao, Fan Wei, Jiahong Lao, Peiyi Zhang, Tianyue Zhao, Dongbei Guo, Qing Han, Honghui Lin, Dawei Zhang","doi":"10.1126/scisignal.aea8478","DOIUrl":"10.1126/scisignal.aea8478","url":null,"abstract":"<div >Plants precisely regulate defense responses to balance energy allocation between growth and immunity. Here, we showed in <i>Arabidopsis thaliana</i> that the homeodomain-leucine zipper protein 1 (HAT1) functions as a redox-controlled mediator that restricts defense responses by competing with the master immune regulator NPR1 for interaction with the transcription factor TGA3. Under normal conditions, oxidative modification of HAT1 at Cys<sup>196</sup>, Cys<sup>202</sup>, Cys<sup>242</sup>, and Cys<sup>245</sup> enhanced its binding affinity for TGA3, effectively competing with NPR1 for binding to TGA3 and sequestering TGA3 from target genes to maintain immune suppression. During immune activation in response to a bacterial pathogen, the phytohormone salicylic acid facilitated the reduction of HAT1 by the thioredoxins TRXh3 and TRXh5, thereby destabilizing the HAT1-TGA3 interaction. Salicylic acid also promoted the formation of NPR1-TGA3 complexes that activated defense gene expression. This redox switch mechanism enabled plants to dynamically regulate TGA3 transcriptional activity through reversible redox modification of HAT1. Our findings elucidate how HAT1 serves as a molecular brake to prevent immune overactivation while permitting dynamic response modulation.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"19 929","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147476347","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}

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AI might be the next stage of our natural evolution: A cancer neuroscience perspective 人工智能可能是我们自然进化的下一个阶段：癌症神经科学的观点。

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-03-10 DOI: 10.1126/scisignal.aeg1158

Ihsan Ekin Demir, Carmen Mota Reyes, Maximilian Berlet, Elke Demir, Ibrahim Halil Gürcinar, Güralp O. Ceyhan, Helmut Friess, Rouzanna Istvanffy, Dirk Felix Wilhelm

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Sense and stromal density 感觉和基质密度。

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-03-10 DOI: 10.1126/scisignal.aeg9266

Leslie K. Ferrarelli

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Human and mouse long noncoding RNAs reengineered for exogenous delivery reduce LPS-induced inflammation in human macrophages and mice 重组外源性递送的人类和小鼠长链非编码rna可减少lps诱导的人类巨噬细胞和小鼠炎症。

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-03-10 DOI: 10.1126/scisignal.adx2924

Janice Pang, Yan Ming Anson Lau, Fabiha Mahbub, Grayson Tilstra, Avery Kemble, Meng Qi Jiang, Yikai Sun, Karlene L. M. Knaggs, Tao Wang, Julien Couture-Senécal, Omar F. Khan

{"title":"Human and mouse long noncoding RNAs reengineered for exogenous delivery reduce LPS-induced inflammation in human macrophages and mice","authors":"Janice Pang, Yan Ming Anson Lau, Fabiha Mahbub, Grayson Tilstra, Avery Kemble, Meng Qi Jiang, Yikai Sun, Karlene L. M. Knaggs, Tao Wang, Julien Couture-Senécal, Omar F. Khan","doi":"10.1126/scisignal.adx2924","DOIUrl":"10.1126/scisignal.adx2924","url":null,"abstract":"<div >Long noncoding RNAs (lncRNAs) constitute a substantial portion of the transcriptome and outnumber protein-coding transcripts in humans. lncRNA molecules are bioactive and control cellular and systemic functions by directly or indirectly regulating gene expression at the transcriptional or posttranscriptional levels. Here, we established the use of lncRNA as a modality to treat disease by reengineering three lncRNAs—GAPLINC, MIST, and DRAIR—to treat acute inflammation in mice and human macrophages. For each lncRNA, we established an in vitro transcription synthesis and high-performance liquid chromatography purification workflow and optimized the lncRNA isoforms, 5′ cap, 3′ poly(A) tail, and chemical base modifications to improve specificity and performance. We also optimized the in vivo delivery of lncRNA with a lipid nanoparticle system that did not induce confounding effects. Using this pipeline and delivery platform, we demonstrated that each lncRNA reduced lipopolysaccharide (LPS)–induced inflammation by specifically regulating distinct subsets of cytokines in cultured mouse macrophages and in mice. GAPLINC and DRAIR reduced the transcription of IL-1β and IL-6, respectively, whereas MIST attenuated TNFα production posttranscriptionally. In addition, we showed that reengineered GAPLINC reduced LPS-induced inflammation in human monocytes, suggesting the clinical potential of this approach. Our engineering approach and findings establish a previously unidentified nucleic acid modality and demonstrate an effective way to reengineer regulatory lncRNAs to treat disease.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"19 928","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436945","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}

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Glucose metabolism sustains aberrant STAT3 signaling in colorectal cancer through glycosylated local signaling factors 葡萄糖代谢通过糖基化的局部信号因子维持结直肠癌中异常的STAT3信号

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-03-03

Kathryn Buscher, Kelsey Temprine, Christopher Mays, Noora Aabed, Samuel A. Kerk, Hannah N. Bell, Joseph A. Nieto Carrion, Harrison S. Greenbaum, Zheng Hong Lee, Varun Ponnusamy, Sadeesh K. Ramakrishnan, Costas A. Lyssiotis, Xiang Xue, Yatrik M. Shah

{"title":"Glucose metabolism sustains aberrant STAT3 signaling in colorectal cancer through glycosylated local signaling factors","authors":"Kathryn Buscher, Kelsey Temprine, Christopher Mays, Noora Aabed, Samuel A. Kerk, Hannah N. Bell, Joseph A. Nieto Carrion, Harrison S. Greenbaum, Zheng Hong Lee, Varun Ponnusamy, Sadeesh K. Ramakrishnan, Costas A. Lyssiotis, Xiang Xue, Yatrik M. Shah","doi":"","DOIUrl":"","url":null,"abstract":"<div >The JAK-STAT3 signaling pathway is a key driver of colorectal cancer (CRC) progression. STAT3 is a transcription factor that is canonically activated by cytokines, such as IL-6, in a transient manner because of negative feedback mechanisms. However, STAT3 is aberrantly and persistently activated in CRC, promoting tumor cell proliferation and survival. Here, we demonstrated that glucose sustained STAT3 activation independently of cytokine availability. We manipulated glucose metabolism, which showed that both glucose and its downstream metabolite GlcNAc were essential to maintain STAT3 activation. Moreover, cells with high basal STAT3 activity produced proteins that were glycosylated in a glucose-dependent manner and that activated STAT3 in neighboring cells through paracrine signaling. Proteomic analysis identified multiple candidate proteins involved in this process; however, no single protein was sufficient to fully activate STAT3, suggesting that this activation process requires several glycosylated proteins. In a syngeneic mouse model of CRC, inhibition of glycolysis reduced STAT3 activation in tumors, and genetic deletion of STAT3 substantially decreased tumor growth. Together, these findings show how glucose metabolism supports sustained STAT3 activation in CRC, highlighting a potential metabolic vulnerability for therapeutic targeting.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"19 927","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147342977","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}

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Hour-scale single-molecule imaging reveals dynamic assembly of the Wnt co-receptors LRP6 and ROR2 into common signalosomes 小时尺度的单分子成像揭示了Wnt共受体LRP6和ROR2在共同信号小体中的动态组装

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-03-03

Michael Philippi, Julia Dohle, Isabelle Watrinet, Michael Holtmannspötter, Yi Miao, Jinye Li, Oliver Birkholz, Ulrich Rothbauer, K. Christopher Garcia, Rainer Kurre, Jacob Piehler, Changjiang You

{"title":"Hour-scale single-molecule imaging reveals dynamic assembly of the Wnt co-receptors LRP6 and ROR2 into common signalosomes","authors":"Michael Philippi, Julia Dohle, Isabelle Watrinet, Michael Holtmannspötter, Yi Miao, Jinye Li, Oliver Birkholz, Ulrich Rothbauer, K. Christopher Garcia, Rainer Kurre, Jacob Piehler, Changjiang You","doi":"","DOIUrl":"","url":null,"abstract":"<div >Wnt ligands stimulate β-catenin–dependent (canonical) or β-catenin–independent (noncanonical) signaling, depending on which co-receptors are recruited to the Wnt receptor FZD. Both pathways are initiated by receptor oligomerization into signalosomes and involve a largely overlapping set of downstream effectors. To resolve the assembly of Wnt signalosomes with high spatiotemporal resolution for extended times, we developed single-molecule tracking and localization microscopy based on labeling with reversibly binding nanobodies (rbTALM). We engineered nanobody-tag pairs with finely tuned binding affinities to ensure single-molecule tracking with high fidelity while also permitting continuous exchange of photobleached labels. Multicolor rbTALM imaging enabled simultaneous tracking and super-resolution imaging of three different tagged Wnt co-receptors in the same cell for more than 1 hour at video rate. Time-lapse correlation analyses uncovered cooperative association of canonical (LRP6) and noncanonical (ROR2) Wnt co-receptors with FZD8 into a common, hybrid Wnt signalosome. These findings demonstrate the potential for rbTALM imaging for exploring nanoscale dynamics across millisecond to hour timescales and for deciphering the molecular dynamics that underlie signaling complex formation.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"19 927","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147342976","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

Acetate enhances long-term memory in female mice by sex-, context-, and brain region–specific epigenetic and transcriptional remodeling 醋酸酯通过性别、环境和脑区域特异性表观遗传和转录重塑增强雌性小鼠的长期记忆

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-02-24

Erica M. Periandri, Kala M. Dodson, Francisca N. de Luna Vitorino, Benjamin A. Garcia, Karl M. Glastad, Gabor Egervari

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Metabolic alterations after traumatic neural injury: Mechanistic insights and potential translational targets for axon regeneration 创伤性神经损伤后的代谢改变：轴突再生的机制见解和潜在的翻译靶点

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-02-24

Qianqian Cao, Wenwen Zhao, Junjie Yan, Stephane Belin, Bin Yu, Homaira Nawabi, Susu Mao

{"title":"Metabolic alterations after traumatic neural injury: Mechanistic insights and potential translational targets for axon regeneration","authors":"Qianqian Cao, Wenwen Zhao, Junjie Yan, Stephane Belin, Bin Yu, Homaira Nawabi, Susu Mao","doi":"","DOIUrl":"","url":null,"abstract":"<div >Metabolism not only provides essential substances and energy for cells through catabolism and anabolism but also exerts broader regulatory roles through metabolic enzymes and products that influence gene expression, thereby maintaining homeostasis. Upon neuronal injury, metabolic changes in both neurons and supporting cells influence neuronal survival and regeneration by regulating energy supply, substrate availability, regeneration-related gene expression, and cell-cell metabolic interactions. Axon regeneration is a key process in neural repair after injury. Beyond the nervous system itself, systemic factors such as diet, exercise, circadian rhythms, and psychological stress also play crucial roles in axon regeneration through interorgan metabolic communication and microbiota-host metabolic cross-talk. In this Review, we summarize advances in understanding metabolic alterations during axon regeneration, with a focus on glycometabolism, lipid metabolism, protein degradation, mitochondrial activity, and systemic factor–driven metabolic cross-talk between nervous and non-nervous systems. We also highlight the therapeutic potential of metabolites themselves, analyze distinct metabolic responses after injury in the peripheral and central nervous systems, and discuss their spatiotemporal dynamics and cell type specificity. Last, we propose that successful neural repair requires the establishment of a systemic pro-regenerative state throughout the entire body.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"19 926","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275144","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}

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Temporal proteomic and phosphoproteomic dynamics during neuronal differentiation in the reference iPSC line KOLF2.1J 参考iPSC细胞系KOLF2.1J神经元分化过程中的时间蛋白质组学和磷酸化蛋白质组学动态

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-02-24

Ying Hao, Ziyi Li, Erika Lara, Daniel M. Ramos, Marianita Santiana, Benjamin Jin, Jacob Epstein, Isabelle Kowal, Jasmin Camacho, Nicole Carmiol, Jae-Hyeon Park, Aleksandra Beylina, Linda G. Yang, Jessica T. Root, Dylan C. Sacks, Paige Jarreau, Cory A. Weller, Sydney Klaisner, Laurel A. Screven, Caroline B. Pantazis, Mike A. Nalls, Priyanka Narayan, Luigi Ferrucci, Andrew B. Singleton, Michael E. Ward, Mark R. Cookson, Yue Andy Qi

{"title":"Temporal proteomic and phosphoproteomic dynamics during neuronal differentiation in the reference iPSC line KOLF2.1J","authors":"Ying Hao, Ziyi Li, Erika Lara, Daniel M. Ramos, Marianita Santiana, Benjamin Jin, Jacob Epstein, Isabelle Kowal, Jasmin Camacho, Nicole Carmiol, Jae-Hyeon Park, Aleksandra Beylina, Linda G. Yang, Jessica T. Root, Dylan C. Sacks, Paige Jarreau, Cory A. Weller, Sydney Klaisner, Laurel A. Screven, Caroline B. Pantazis, Mike A. Nalls, Priyanka Narayan, Luigi Ferrucci, Andrew B. Singleton, Michael E. Ward, Mark R. Cookson, Yue Andy Qi","doi":"","DOIUrl":"","url":null,"abstract":"<div >Induced pluripotent stem cell (iPSC)–derived neurons are a powerful tool with which to investigate both neuronal development and neurodegenerative diseases. Here, we applied quantitative proteomic and phosphoproteomic analyses to profile the neuronal differentiation of the KOLF2.1J iPSC line, the first reference line of the iPSC Neurodegenerative Disease Initiative (iNDI) project. We developed an automated workflow enabling high-coverage enrichment of proteins and phosphorylated peptides, which revealed molecular signatures during the differentiation of iPSC-derived neurons. Proteomic data highlighted distinct changes in mitochondrial pathways throughout the course of differentiation, whereas phosphoproteomic data revealed specific regulatory dynamics in GTPase-mediated signaling pathways and microtubule proteins. Additionally, phosphosite dynamics were not correlated to changes in protein abundance, particularly in processes related to axon functions and RNA transport. We measured the dynamic changes in kinases that are critical for neuronal development and maturation and developed an interactive web app to visualize the temporal landscape dynamics of protein and phosphosite abundance. By establishing baselines of proteomic and phosphoproteomic profiles for neuronal differentiation, this dataset is a valuable resource for future research into neuronal development and neurodegenerative diseases using this reference iPSC line.</div>","PeriodicalId":21658,"journal":{"name":"Science Signaling","volume":"19 926","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275119","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}

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Fungi facilitate gut healing 真菌促进肠道愈合

IF 6.6 1区生物学

Science Signaling Pub Date : 2026-02-24

Annalisa M. VanHook

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