Cell Chemical Biology最新文献_第8页

The art of designed coiled-coils for the regulation of mammalian cells 设计用于调节哺乳动物细胞的盘绕线圈的艺术。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.06.001

{"title":"The art of designed coiled-coils for the regulation of mammalian cells","authors":"","doi":"10.1016/j.chembiol.2024.06.001","DOIUrl":"10.1016/j.chembiol.2024.06.001","url":null,"abstract":"<div><p>Synthetic biology aims to engineer complex biological systems using modular elements, with coiled-coil (CC) dimer-forming modules are emerging as highly useful building blocks in the regulation of protein assemblies and biological processes. Those small modules facilitate highly specific and orthogonal protein-protein interactions, offering versatility for the regulation of diverse biological functions. Additionally, their design rules enable precise control and tunability over these interactions, which are crucial for specific applications. Recent advancements showcase their potential for use in innovative therapeutic interventions and biomedical applications. In this review, we discuss the potential of CCs, exploring their diverse applications in mammalian cells, such as synthetic biological circuit design, transcriptional and allosteric regulation, cellular assemblies, chimeric antigen receptor (CAR) T cell regulation, and genome editing and their role in advancing the understanding and regulation of cellular processes.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 8","pages":"Pages 1460-1472"},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624002204/pdfft?md5=85fef3f748d2012ce1eea38d5efda70f&pid=1-s2.0-S2451945624002204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544253","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

Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture 赛普特蛋白通过调控气敏D的裂解和ninjurin-1介导的质膜破裂促进巨噬细胞的脓毒症

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.003

Dominik Brokatzky , Margarida C. Gomes , Stevens Robertin , Carolina Albino , Sydney L. Miles , Serge Mostowy

{"title":"Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture","authors":"Dominik Brokatzky , Margarida C. Gomes , Stevens Robertin , Carolina Albino , Sydney L. Miles , Serge Mostowy","doi":"10.1016/j.chembiol.2024.07.003","DOIUrl":"10.1016/j.chembiol.2024.07.003","url":null,"abstract":"<div><p>The septin cytoskeleton is primarily known for roles in cell division and host defense against bacterial infection. Despite recent insights, the full breadth of roles for septins in host defense is poorly understood. In macrophages, <em>Shigella</em> induces pyroptosis, a pro-inflammatory form of cell death dependent upon gasdermin D (GSDMD) pores at the plasma membrane and cell surface protein ninjurin-1 (NINJ1) for membrane rupture. Here, we discover that septins promote macrophage pyroptosis induced by lipopolysaccharide (LPS)/nigericin and <em>Shigella</em> infection, but do not affect cytokine expression or release. We observe that septin filaments assemble at the plasma membrane, and cleavage of GSDMD is impaired in septin-depleted cells. We found that septins regulate mitochondrial dynamics and the expression of NINJ1. Using a <em>Shigella</em>-zebrafish infection model, we show that septin-mediated pyroptosis is an <em>in vivo</em> mechanism of infection control. The discovery of septins as a mediator of pyroptosis may inspire innovative anti-bacterial and anti-inflammatory treatments.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 8","pages":"Pages 1518-1528.e6"},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003052/pdfft?md5=1fda9bdffaba472fc447836cdbe316e3&pid=1-s2.0-S2451945624003052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892170","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

Regulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies 调控诱导接近靶向嵌合体--RIPTACs--用于癌症选择性疗法的异功能小分子策略

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.005

Kanak Raina , Chris D. Forbes , Rebecca Stronk , Jonathan P. Rappi Jr. , Kyle J. Eastman , Nilesh Zaware , Xinheng Yu , Hao Li , Amit Bhardwaj , Samuel W. Gerritz , Mia Forgione , Abigail Hundt , Madeline P. King , Zoe M. Posner , Allison D. Correia , Andrew McGovern , David E. Puleo , Rebekka Chenard , James J. Mousseau , J. Ignacio Vergara , Craig M. Crews

{"title":"Regulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies","authors":"Kanak Raina , Chris D. Forbes , Rebecca Stronk , Jonathan P. Rappi Jr. , Kyle J. Eastman , Nilesh Zaware , Xinheng Yu , Hao Li , Amit Bhardwaj , Samuel W. Gerritz , Mia Forgione , Abigail Hundt , Madeline P. King , Zoe M. Posner , Allison D. Correia , Andrew McGovern , David E. Puleo , Rebekka Chenard , James J. Mousseau , J. Ignacio Vergara , Craig M. Crews","doi":"10.1016/j.chembiol.2024.07.005","DOIUrl":"10.1016/j.chembiol.2024.07.005","url":null,"abstract":"<div><p>We describe a protein proximity inducing therapeutic modality called Regulated Induced Proximity Targeting Chimeras or RIPTACs: heterobifunctional small molecules that elicit a stable ternary complex between a target protein (TP) selectively expressed in tumor cells and a pan-expressed protein essential for cell survival. The resulting co-operative protein-protein interaction (PPI) abrogates the function of the essential protein, thus leading to death selectively in cells expressing the TP. This approach leverages differentially expressed intracellular proteins as novel cancer targets, with the advantage of not requiring the target to be a disease driver. In this chemical biology study, we design RIPTACs that incorporate a ligand against a model TP connected via a linker to effector ligands such as JQ1 (BRD4) or BI2536 (PLK1) or CDK inhibitors such as TMX3013 or dinaciclib. RIPTACs accumulate selectively in cells expressing the HaloTag-FKBP target, form co-operative intracellular ternary complexes, and induce an anti-proliferative response in target-expressing cells.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 8","pages":"Pages 1490-1502.e42"},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899985","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

AspSnFR: A genetically encoded biosensor for real-time monitoring of aspartate in live cells AspSnFR：用于实时监测活细胞中天冬氨酸的基因编码生物传感器

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.05.002

{"title":"AspSnFR: A genetically encoded biosensor for real-time monitoring of aspartate in live cells","authors":"","doi":"10.1016/j.chembiol.2024.05.002","DOIUrl":"10.1016/j.chembiol.2024.05.002","url":null,"abstract":"<div><p>Aspartate is crucial for nucleotide synthesis, ammonia detoxification, and maintaining redox balance via the malate-aspartate-shuttle (MAS). To disentangle these multiple roles of aspartate metabolism, tools are required that measure aspartate concentrations in real time and in live cells. We introduce AspSnFR, a genetically encoded green fluorescent biosensor for intracellular aspartate, engineered through displaying and screening biosensor libraries on mammalian cells. In live cells, AspSnFR is able to precisely and quantitatively measure cytosolic aspartate concentrations and dissect its production from glutamine. Combining high-content imaging of AspSnFR with pharmacological perturbations exposes differences in metabolic vulnerabilities of aspartate levels based on nutrient availability. Further, AspSnFR facilitates tracking of aspartate export from mitochondria through SLC25A12, the MAS’ key transporter. We show that SLC25A12 is a rapidly responding and direct route to couple Ca<sup>2+</sup> signaling with mitochondrial aspartate export. This establishes SLC25A12 as a crucial link between cellular signaling, mitochondrial respiration, and metabolism.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 8","pages":"Pages 1529-1541.e12"},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400179X/pdfft?md5=3b3153c35af18753feadccb80f236687&pid=1-s2.0-S245194562400179X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156564","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

The chemistry of electrical signaling in sodium channels from bacteria and beyond 细菌等钠离子通道中的电信号化学反应

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.010

William A. Catterall , Tamer M. Gamal El-Din , Goragot Wisedchaisri

{"title":"The chemistry of electrical signaling in sodium channels from bacteria and beyond","authors":"William A. Catterall , Tamer M. Gamal El-Din , Goragot Wisedchaisri","doi":"10.1016/j.chembiol.2024.07.010","DOIUrl":"10.1016/j.chembiol.2024.07.010","url":null,"abstract":"<div><p>Electrical signaling is essential for all fast processes in biology, but its molecular mechanisms have been uncertain. This review article focuses on studies of bacterial sodium channels in order to home in on the essential molecular and chemical mechanisms underlying transmembrane ion conductance and voltage-dependent gating without the overlay of complex protein interactions and regulatory mechanisms in mammalian sodium channels. This minimalist approach has yielded a nearly complete picture of sodium channel function at the atomic level that are mostly conserved in mammalian sodium channels, including sodium selectivity and conductance, voltage sensing and activation, electromechanical coupling to pore opening and closing, slow inactivation, and pathogenic dysfunction in a debilitating channelopathy. Future studies of nature’s simplest sodium channels may continue to yield key insights into the fundamental molecular and chemical principles of their function and further elucidate the chemical basis of electrical signaling.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 8","pages":"Pages 1405-1421"},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400312X/pdfft?md5=0c34706ac158a70d52d3dd2d116ee049&pid=1-s2.0-S245194562400312X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990568","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

Meet the authors: Xueqin Jin, Jian Huang, Huan Wang, Kan Wang, and Nieng Yan 与作者见面金雪琴、黄健、王欢、王侃和严能

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.009

Xueqin Jin, Jian Huang, Huan Wang, Kan Wang, Nieng Yan

引用次数: 0

Synthetic gene circuit evolution: Insights and opportunities at the mid-scale 合成基因回路进化：中等规模的洞察力和机遇

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.05.018

{"title":"Synthetic gene circuit evolution: Insights and opportunities at the mid-scale","authors":"","doi":"10.1016/j.chembiol.2024.05.018","DOIUrl":"10.1016/j.chembiol.2024.05.018","url":null,"abstract":"<div><p>Directed evolution focuses on optimizing single genetic components for predefined engineering goals by artificial mutagenesis and selection. In contrast, experimental evolution studies the adaptation of entire genomes in serially propagated cell populations, to provide an experimental basis for evolutionary theory. There is a relatively unexplored gap at the middle ground between these two techniques, to evolve <em>in vivo</em> entire synthetic gene circuits with nontrivial dynamic function instead of single parts or whole genomes. We discuss the requirements for such mid-scale evolution, with hypothetical examples for evolving synthetic gene circuits by appropriate selection and targeted shuffling of a seed set of genetic components <em>in vivo</em>. Implementing similar methods should aid the rapid generation, functionalization, and optimization of synthetic gene circuits in various organisms and environments, accelerating both the development of biomedical and technological applications and the understanding of principles guiding regulatory network evolution.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 8","pages":"Pages 1447-1459"},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624002198/pdfft?md5=ab725988d0ab4ed2c1198c5281ace930&pid=1-s2.0-S2451945624002198-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448798","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

Therapeutic potential of cis-targeting bispecific antibodies 顺式靶向双特异性抗体的治疗潜力

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.004

Rob C. Oslund , Pamela M. Holland , Scott A. Lesley , Olugbeminiyi O. Fadeyi

引用次数: 0

Carolyn Bertozzi: Building new bonds between molecules, fields, and communities 卡罗琳-贝托兹：在分子、领域和社区之间建立新的联系

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.015

Matthew R. Pratt , Jennifer A. Prescher

引用次数: 0

Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway. 人类 AKR1C3 与 GPR84 的激动剂结合，并参与扩展的多胺途径。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-09 DOI: 10.1016/j.chembiol.2024.07.011

Natavan Dudkina, Hyun Bong Park, Deguang Song, Abhishek Jain, Sajid A Khan, Richard A Flavell, Caroline H Johnson, Noah W Palm, Jason M Crawford

{"title":"Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway.","authors":"Natavan Dudkina, Hyun Bong Park, Deguang Song, Abhishek Jain, Sajid A Khan, Richard A Flavell, Caroline H Johnson, Noah W Palm, Jason M Crawford","doi":"10.1016/j.chembiol.2024.07.011","DOIUrl":"10.1016/j.chembiol.2024.07.011","url":null,"abstract":"<p><p>Altered human aldo-keto reductase family 1 member C3 (AKR1C3) expression has been associated with poor prognosis in diverse cancers, ferroptosis resistance, and metabolic diseases. Despite its clinical significance, the endogenous biochemical roles of AKR1C3 remain incompletely defined. Using untargeted metabolomics, we identified a major transformation mediated by AKR1C3, in which a spermine oxidation product \"sperminal\" is reduced to \"sperminol.\" Sperminal causes DNA damage and activates the DNA double-strand break response, whereas sperminol induces autophagy in vitro. AKR1C3 also pulls down acyl-pyrones and pyrone-211 inhibits AKR1C3 activity. Through G protein-coupled receptor ligand screening, we determined that pyrone-211 is also a potent agonist of the semi-orphan receptor GPR84. Strikingly, mammalian fatty acid synthase produces acyl-pyrones in vitro, and this production is modulated by NADPH. Taken together, our studies support a regulatory role of AKR1C3 in an expanded polyamine pathway and a model linking fatty acid synthesis and NADPH levels to GPR84 signaling.</p>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007975","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