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Mechanistic insights into gasdermin-mediated pyroptosis 气凝胶介导的焦亡机制
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-03-24 DOI: 10.1038/s41580-025-00837-0
Yang Bai, Youdong Pan, Xing Liu
{"title":"Mechanistic insights into gasdermin-mediated pyroptosis","authors":"Yang Bai, Youdong Pan, Xing Liu","doi":"10.1038/s41580-025-00837-0","DOIUrl":"https://doi.org/10.1038/s41580-025-00837-0","url":null,"abstract":"<p>Pyroptosis, a novel mode of inflammatory cell death, is executed by membrane pore-forming gasdermin (GSDM) family members in response to extracellular or intracellular injury cues and is characterized by a ballooning cell morphology, plasma membrane rupture and the release of inflammatory mediators such as interleukin-1β (IL-1β), IL-18 and high mobility group protein B1 (HMGB1). It is a key effector mechanism for host immune defence and surveillance against invading pathogens and aberrant cancerous cells, and contributes to the onset and pathogenesis of inflammatory and autoimmune diseases. Manipulating the pore-forming activity of GSDMs and pyroptosis could lead to novel therapeutic strategies. In this Review, we discuss the current knowledge regarding how GSDM-mediated pyroptosis is initiated, executed and regulated, its roles in physiological and pathological processes, and the crosstalk between different modes of programmed cell death. We also highlight the development of drugs that target pyroptotic pathways for disease treatment.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"16 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677649","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
Nuclear and genome dynamics underlying DNA double-strand break repair DNA双链断裂修复背后的核和基因组动力学
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-03-17 DOI: 10.1038/s41580-025-00828-1
Irene Chiolo, Matthias Altmeyer, Gaëlle Legube, Karim Mekhail
{"title":"Nuclear and genome dynamics underlying DNA double-strand break repair","authors":"Irene Chiolo, Matthias Altmeyer, Gaëlle Legube, Karim Mekhail","doi":"10.1038/s41580-025-00828-1","DOIUrl":"https://doi.org/10.1038/s41580-025-00828-1","url":null,"abstract":"<p>Changes in nuclear shape and in the spatial organization of chromosomes in the nucleus commonly occur in cancer, ageing and other clinical contexts that are characterized by increased DNA damage. However, the relationship between nuclear architecture, genome organization, chromosome stability and health remains poorly defined. Studies exploring the connections between the positioning and mobility of damaged DNA relative to various nuclear structures and genomic loci have revealed nuclear and cytoplasmic processes that affect chromosome stability. In this Review, we discuss the dynamic mechanisms that regulate nuclear and genome organization to promote DNA double-strand break (DSB) repair, genome stability and cell survival. Genome dynamics that support DSB repair rely on chromatin states, repair-protein condensates, nuclear or cytoplasmic microtubules and actin filaments, kinesin or myosin motor proteins, the nuclear envelope, various nuclear compartments, chromosome topology, chromatin loop extrusion and diverse signalling cues. These processes are commonly altered in cancer and during natural or premature ageing. Indeed, the reshaping of the genome in nuclear space during DSB repair points to new avenues for therapeutic interventions that may take advantage of new cancer cell vulnerabilities or aim to reverse age-associated defects.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"17 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640384","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
Modes of Notch signalling in development and disease Notch信号在发育和疾病中的模式
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-03-10 DOI: 10.1038/s41580-025-00835-2
Sarah J. Bray, Anna Bigas
{"title":"Modes of Notch signalling in development and disease","authors":"Sarah J. Bray, Anna Bigas","doi":"10.1038/s41580-025-00835-2","DOIUrl":"https://doi.org/10.1038/s41580-025-00835-2","url":null,"abstract":"<p>Many different animal developmental and homeostatic processes rely on signalling via the highly conserved Notch pathway. Often Notch signalling has iterative roles during cell specification and differentiation, controlling not only the state of progenitor cells but also the fate and function of their progeny. Its roles continue throughout the lifespan of the organism, regulating normal tissue maintenance, as well as operating in response to damage. Consistent with such fundamental roles, the pathway has been associated with numerous diseases, including cancers. Understanding how Notch signalling is orchestrated to bring about different outcomes is challenging, given that it has many diverse functions. Classic models proposed that stochastic differences in cell states were important to polarise signalling during cell fate decisions. Subsequently, the importance of oscillatory Notch signalling was uncovered, and it became clear that it operates in different modalities depending on the regulatory inputs. With the advent of ever-more-sensitive live-imaging and quantitative approaches, it is becoming evident that differences in the dynamics, levels and architectures of Notch signalling are critical in shaping and maintaining tissues. This Review focuses on the cellular and molecular mechanisms involved in conferring different modalities on Notch pathway operations and how these enable different types of functional outcomes from pathway activation. We also discuss their dysregulation in cancer.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"15 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582963","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
CRISPR–Cas applications in agriculture and plant research CRISPR-Cas在农业和植物研究中的应用
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-03-07 DOI: 10.1038/s41580-025-00834-3
Aytug Tuncel, Changtian Pan, Joshua S. Clem, Degao Liu, Yiping Qi
{"title":"CRISPR–Cas applications in agriculture and plant research","authors":"Aytug Tuncel, Changtian Pan, Joshua S. Clem, Degao Liu, Yiping Qi","doi":"10.1038/s41580-025-00834-3","DOIUrl":"https://doi.org/10.1038/s41580-025-00834-3","url":null,"abstract":"<p>Growing world population and deteriorating climate conditions necessitate the development of new crops with high yields and resilience. CRISPR–Cas-mediated genome engineering presents unparalleled opportunities to engineer crop varieties cheaper, easier and faster than ever. In this Review, we discuss how the CRISPR–Cas toolbox has rapidly expanded from Cas9 and Cas12 to include different Cas orthologues and engineered variants. We present various CRISPR–Cas-based methods, including base editing and prime editing, which are used for precise genome, epigenome and transcriptome engineering, and methods used to deliver the genome editors into plants, such as bacterial-mediated and viral-mediated transformation. We then discuss how promoter editing and chromosome engineering are used in crop breeding for trait engineering and fixation, and important applications of CRISPR–Cas in crop improvement, such as de novo domestication and enhancing tolerance to abiotic stresses. We conclude with discussing future prospects of plant genome engineering.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"49 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569572","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
Dodging mitochondrial mislocalization 避免线粒体错位
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-03-06 DOI: 10.1038/s41580-025-00840-5
Lisa Heinke
{"title":"Dodging mitochondrial mislocalization","authors":"Lisa Heinke","doi":"10.1038/s41580-025-00840-5","DOIUrl":"10.1038/s41580-025-00840-5","url":null,"abstract":"Subunits of mitochondrial and cytosolic ribosomes need to be targeted to their correction cellular location. A study identified a mitochondrial avoidance segment in a eukaryotic cytosolic ribosome subunit that prevents its mislocalization to mitochondria.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 4","pages":"253-253"},"PeriodicalIF":81.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560754","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
In tumour suppressors, synonymous is not always silent 在肿瘤抑制因子中，同义词并不总是沉默的
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-03-03 DOI: 10.1038/s41580-025-00838-z
Michael Attwaters
{"title":"In tumour suppressors, synonymous is not always silent","authors":"Michael Attwaters","doi":"10.1038/s41580-025-00838-z","DOIUrl":"10.1038/s41580-025-00838-z","url":null,"abstract":"Synonymous mutations can promote tumorigenesis by perturbing m6A modification of tumour suppressor mRNAs.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 4","pages":"254-254"},"PeriodicalIF":81.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538620","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
Improving chemical reprogramming strategies 改进化学重编程策略
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-02-17 DOI: 10.1038/s41580-025-00836-1
Yanglu Wang, Lin Cheng
{"title":"Improving chemical reprogramming strategies","authors":"Yanglu Wang,&nbsp;Lin Cheng","doi":"10.1038/s41580-025-00836-1","DOIUrl":"10.1038/s41580-025-00836-1","url":null,"abstract":"In this Tools of the Trade article, Wang and Cheng (Deng Lab) describe an improved protocol for the generation of human pluripotent stem cells by chemical reprogramming based on the targeting of epigenetic obstacles.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 5","pages":"333-333"},"PeriodicalIF":81.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435205","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
Profiling the disordered proteome in cells using a chemical tag 利用化学标签分析细胞中紊乱的蛋白质组。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-02-13 DOI: 10.1038/s41580-025-00833-4
Tze Cin Owyong, Shouxiang Zhang
{"title":"Profiling the disordered proteome in cells using a chemical tag","authors":"Tze Cin Owyong,&nbsp;Shouxiang Zhang","doi":"10.1038/s41580-025-00833-4","DOIUrl":"10.1038/s41580-025-00833-4","url":null,"abstract":"In this Tools of the Trade article, Zhang and Owyong (Hong lab) discuss the development of a fluorescent probe that binds disordered proteins in situ and allows their enrichment and identification using a mass-spectrometry-based workflow.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 5","pages":"334-334"},"PeriodicalIF":81.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414665","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
Regulation and function of insulin and insulin-like growth factor receptor signalling
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-02-10 DOI: 10.1038/s41580-025-00826-3
Eunhee Choi, Cunming Duan, Xiao-chen Bai
{"title":"Regulation and function of insulin and insulin-like growth factor receptor signalling","authors":"Eunhee Choi, Cunming Duan, Xiao-chen Bai","doi":"10.1038/s41580-025-00826-3","DOIUrl":"https://doi.org/10.1038/s41580-025-00826-3","url":null,"abstract":"<p>Receptors of insulin and insulin-like growth factors (IGFs) are receptor tyrosine kinases whose signalling controls multiple aspects of animal physiology throughout life. In addition to regulating metabolism and growth, insulin–IGF receptor signalling has recently been linked to a variety of new, cell type-specific functions. In the last century, key questions have focused on how structural differences of insulin and IGFs affect receptor activation, and how insulin–IGF receptor signalling translates into pleiotropic biological functions. Technological advances such as cryo-electron microscopy have provided a detailed understanding of how native and engineered ligands activate insulin–IGF receptors. In this Review, we highlight recent structural and functional insights into the activation of insulin–IGF receptors, and summarize new agonists and antagonists developed for intervening in the activation of insulin–IGF receptor signalling. Furthermore, we discuss recently identified regulatory mechanisms beyond ligand–receptor interactions and functions of insulin–IGF receptor signalling in diseases.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"162 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385074","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 bystander effect of pyroptosis
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-02-04 DOI: 10.1038/s41580-025-00831-6
Lisa Heinke
{"title":"The bystander effect of pyroptosis","authors":"Lisa Heinke","doi":"10.1038/s41580-025-00831-6","DOIUrl":"10.1038/s41580-025-00831-6","url":null,"abstract":"This study uncovered how extracellular vesicles carrying gasdermin D pores propagate pyroptosis between cells, exacerbating inflammation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"174-174"},"PeriodicalIF":81.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083416","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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