Cell Chemical Biology最新文献

Microbiota mechanisms in cancer progression and therapy 微生物群在癌症进展和治疗中的机制

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-06 DOI: 10.1016/j.chembiol.2025.04.005

Xing Zhang, Kyong Tkhe Fam, Tingting Dai, Howard C. Hang

引用次数: 0

Integrative proximal-ubiquitomics profiling for deubiquitinase substrate discovery applied to USP30 应用于USP30去泛素酶底物发现的综合近端泛素组学分析

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-05 DOI: 10.1016/j.chembiol.2025.04.004

Andreas Damianou, Hannah B.L. Jones, Athina Grigoriou, Mohammed A. Akbor, Edward Jenkins, Philip D. Charles, Iolanda Vendrell, Simon Davis, Benedikt M. Kessler

{"title":"Integrative proximal-ubiquitomics profiling for deubiquitinase substrate discovery applied to USP30","authors":"Andreas Damianou, Hannah B.L. Jones, Athina Grigoriou, Mohammed A. Akbor, Edward Jenkins, Philip D. Charles, Iolanda Vendrell, Simon Davis, Benedikt M. Kessler","doi":"10.1016/j.chembiol.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.chembiol.2025.04.004","url":null,"abstract":"The growing interest in deubiquitinases (DUBs) as drug targets for modulating critical molecular pathways in disease is fueled by the discovery of their specific cellular roles. A crucial aspect of this fact is the identification of DUB substrates. While mass spectrometry-based proteomic methods can be used to study global changes in cellular ubiquitination following DUB activity perturbation, these datasets often include indirect and downstream ubiquitination events. To enrich for the direct substrates of DUB enzymes, we have developed a proximal-ubiquitome workflow that combines proximity labeling methodology (ascorbate peroxidase-2 [APEX2]) with subsequent ubiquitination enrichment based on the K-ε-GG motif. We applied this technology to identify altered ubiquitination events in the vicinity of the DUB ubiquitin-specific protease 30 (USP30) upon its inhibition. Our findings reveal ubiquitination events previously associated with USP30 on TOMM20 and FKBP8, as well as the candidate substrate LETM1, which is deubiquitinated in a USP30-dependent manner.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"48 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905662","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

MapID-based quantitative mapping of chemical modifications and expression of human transfer RNA 基于mapid的人转移RNA的化学修饰和表达定量图谱

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-02 DOI: 10.1016/j.chembiol.2025.04.003

Mitchel L. Tepe, Yitan Chen, Allison Carso, Huiqing Zhou

{"title":"MapID-based quantitative mapping of chemical modifications and expression of human transfer RNA","authors":"Mitchel L. Tepe, Yitan Chen, Allison Carso, Huiqing Zhou","doi":"10.1016/j.chembiol.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.chembiol.2025.04.003","url":null,"abstract":"Detection and quantification of tRNA chemical modifications are critical for understanding their regulatory functions in biology and diseases. However, tRNA-seq–based methods for modification mapping encountered challenges both experimentally (poor processivity of heavily modified tRNAs during reverse transcription or RT) and bioinformatically (frequent reads misalignment to highly similar tRNA genes). Here, we report “MapID-tRNA-seq” where we deployed an evolved reverse transcriptase (RT-1306) into tRNA-seq and developed “MapIDs” that reduce redundancy of the human tRNA genome and explicitly annotate genetic variances. RT-1306 generated robust mutations against m<sup>1</sup>A and m<sup>3</sup>C, and RT stops against multiple bulky roadblock modifications. MapID-assisted data processing enabled systematic exclusion of false-positive discoveries of modifications which arise from reads misalignment onto similar genes. We applied MapID-tRNA-seq into mapping m<sup>1</sup>A, m<sup>3</sup>C and expression levels of tRNAs in three mammary cell lines, which revealed cell-type dependent modification sites and potential translational regulation of the reduced mitochondrial activities in breast cancer.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"48 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897780","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

N-acetyl-l-cysteine averts ferroptosis by fostering glutathione peroxidase 4 n -乙酰-l-半胱氨酸通过促进谷胱甘肽过氧化物酶4来避免铁下垂

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-30 DOI: 10.1016/j.chembiol.2025.04.002

Jiashuo Zheng, Weijia Zhang, Junya Ito, Bernhard Henkelmann, Chenxi Xu, Eikan Mishima, Marcus Conrad

{"title":"N-acetyl-l-cysteine averts ferroptosis by fostering glutathione peroxidase 4","authors":"Jiashuo Zheng, Weijia Zhang, Junya Ito, Bernhard Henkelmann, Chenxi Xu, Eikan Mishima, Marcus Conrad","doi":"10.1016/j.chembiol.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.chembiol.2025.04.002","url":null,"abstract":"<em>N</em>-acetyl-<span>l</span>-cysteine (NAC) is a medication and a widely used antioxidant in cell death research. Despite its somewhat obscure mechanism of action, its role in inhibiting ferroptosis is gaining increasing recognition. In this study, we demonstrate that NAC treatment rapidly replenishes the intracellular cysteine pool, reinforcing its function as a prodrug for cysteine. Interestingly, its enantiomer, <em>N</em>-acetyl-<span>d</span>-cysteine (<span>d</span>-NAC), which cannot be converted into cysteine, also exhibits a strong anti-ferroptotic effect. We further clarify that NAC, <span>d</span>-NAC, and cysteine all act as direct reducing substrates for GPX4, counteracting lipid peroxidation. Consequently, only GPX4—rather than system x<sub>c</sub><sup>−</sup>, glutathione biosynthesis, or ferroptosis suppressor protein 1—is necessary for NAC and <span>d</span>-NAC to prevent ferroptosis. Additionally, we identify a broad range of reducing substrates for GPX4 <em>in vitro</em>, including β-mercaptoethanol. These findings provide new insights into the mechanisms underlying the protective effects of NAC and other potential GPX4-reducing substrates against ferroptosis.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"43 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889940","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

Impact of radiation therapy on the immunological tumor microenvironment 放射治疗对肿瘤免疫微环境的影响

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-24 DOI: 10.1016/j.chembiol.2025.04.001

Emma Guilbaud, Flavie Naulin, Lydia Meziani, Eric Deutsch, Lorenzo Galluzzi

引用次数: 0

Genetically encoded tool for manipulation of ΔΨm identifies its role as the driver of ISR induced by ATP synthase dysfunction 操纵ΔΨm的遗传编码工具确定其作为ATP合酶功能障碍诱导的ISR驱动因素的作用

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-17 DOI: 10.1016/j.chembiol.2025.03.007

Mangyu Choe , Alex E. Ekvik , Gretchen Stalnaker , Hijai R. Shin , Denis V. Titov

引用次数: 0

Engineering electrogenetic interfaces for mammalian cell control 哺乳动物细胞控制的电基因界面工程学

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-17 DOI: 10.1016/j.chembiol.2025.01.003

Maysam Mansouri , Martin Fussenegger

引用次数: 0

Targeted degradation of CDK9 potently disrupts the MYC-regulated network CDK9的靶向降解可能会破坏myc调控的网络

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-17 DOI: 10.1016/j.chembiol.2025.03.001

Mohammed A. Toure , Keisuke Motoyama , Yichen Xiang , Julie Urgiles , Florian Kabinger , Ann-Sophie Koglin , Ramya S. Iyer , Kaitlyn Gagnon , Amruth Kumar , Samuel Ojeda , Drew A. Harrison , Matthew G. Rees , Jennifer A. Roth , Christopher J. Ott , Richard Schiavoni , Charles A. Whittaker , Stuart S. Levine , Forest M. White , Eliezer Calo , Andre Richters , Angela N. Koehler

{"title":"Targeted degradation of CDK9 potently disrupts the MYC-regulated network","authors":"Mohammed A. Toure , Keisuke Motoyama , Yichen Xiang , Julie Urgiles , Florian Kabinger , Ann-Sophie Koglin , Ramya S. Iyer , Kaitlyn Gagnon , Amruth Kumar , Samuel Ojeda , Drew A. Harrison , Matthew G. Rees , Jennifer A. Roth , Christopher J. Ott , Richard Schiavoni , Charles A. Whittaker , Stuart S. Levine , Forest M. White , Eliezer Calo , Andre Richters , Angela N. Koehler","doi":"10.1016/j.chembiol.2025.03.001","DOIUrl":"10.1016/j.chembiol.2025.03.001","url":null,"abstract":"<div><div>CDK9 coordinates signaling events that regulate transcription and is implicated in oncogenic pathways, making it an actionable target for drug development. While numerous CDK9 inhibitors have been developed, success in the clinic has been limited. Targeted degradation offers a promising alternative. A comprehensive evaluation of degradation versus inhibition is needed to assess when degradation might offer superior therapeutic outcomes. We report a selective and potent CDK9 degrader with rapid kinetics, comparing its downstream effects to those of a conventional inhibitor. We validated that CDK9 inhibition triggers a compensatory feedback mechanism that dampens its anticipated effect on MYC expression and found that this was absent when degraded. Importantly, degradation is more effective at disrupting MYC transcriptional regulation and subsequently destabilizing nucleolar homeostasis, likely by abrogation of both enzymatic and scaffolding functions of CDK9. These findings suggest that CDK9 degradation offers a more robust strategy to overcome limitations associated with its inhibition.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 542-555.e10"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713581","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

Natural products chlorotonils exert a complex antibacterial mechanism and address multiple targets 天然产物氯通体具有复杂的抗菌机制和多靶点

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-17 DOI: 10.1016/j.chembiol.2025.03.005

Felix Deschner , Dietrich Mostert , Jan-Martin Daniel , Alexander Voltz , Dana Carina Schneider , Navid Khangholi , Jürgen Bartel , Laís Pessanha de Carvalho , Madita Brauer , Tatiana E. Gorelik , Christian Kleeberg , Timo Risch , F.P. Jake Haeckl , Laura Herraiz Benítez , Anastasia Andreas , Andreas Martin Kany , Gwenaëlle Jézéquel , Walter Hofer , Mathias Müsken , Jana Held , Jennifer Herrmann

{"title":"Natural products chlorotonils exert a complex antibacterial mechanism and address multiple targets","authors":"Felix Deschner , Dietrich Mostert , Jan-Martin Daniel , Alexander Voltz , Dana Carina Schneider , Navid Khangholi , Jürgen Bartel , Laís Pessanha de Carvalho , Madita Brauer , Tatiana E. Gorelik , Christian Kleeberg , Timo Risch , F.P. Jake Haeckl , Laura Herraiz Benítez , Anastasia Andreas , Andreas Martin Kany , Gwenaëlle Jézéquel , Walter Hofer , Mathias Müsken , Jana Held , Jennifer Herrmann","doi":"10.1016/j.chembiol.2025.03.005","DOIUrl":"10.1016/j.chembiol.2025.03.005","url":null,"abstract":"<div><div>Antimicrobial resistance is a threat to human health rendering current first-line antibiotics ineffective. New agents overcoming resistance mechanisms are urgently needed to guarantee successful treatment of human disease in the future. Chlorotonils, a natural product class with yet unknown mode of action, were shown to have broad-spectrum activity against multi-resistant Gram-positive bacteria and the malaria parasite <em>Plasmodium falciparum,</em> with promising activity and safety in murine infection models. Here, we report that chlorotonils can target the cell membrane, cell wall, and protein biosynthesis. They can be characterized by a rapid onset of action via interference with ion homeostasis leading to membrane depolarization, however, without inducing severe barrier failure or cellular lysis. Further characterization confirmed binding of chlorotonils to bacterial membrane lipids eventually leading to uncontrolled potassium transport. Additionally, we identified functional inhibition of the peptidoglycan biosynthesis protein YbjG and methionine aminopeptidase MetAP as secondary targets of chlorotonils.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 586-602.e15"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798015","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

Streptomycin targets tumor-initiating cells by disrupting oxidative phosphorylation 链霉素通过破坏氧化磷酸化靶向肿瘤启动细胞

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-04-17 DOI: 10.1016/j.chembiol.2025.03.008

Hélène Guillorit , Sébastien Relier , Benjamin Zagiel , Audrey Di Giorgio , Chris Planque , Bastien Felipe , Hélène Hérault , Lucile Bansard , Céline Bouclier , Béatrice Chabi , François Casas , Ornella Clara , Béatrice Bonafos , Xavier Mialhe , Chantal Cazevieille , Szimonetta Hideg , Armelle Choquet , Amandine Bastide , Julie Pannequin , Maria Duca , Alexandre David

{"title":"Streptomycin targets tumor-initiating cells by disrupting oxidative phosphorylation","authors":"Hélène Guillorit , Sébastien Relier , Benjamin Zagiel , Audrey Di Giorgio , Chris Planque , Bastien Felipe , Hélène Hérault , Lucile Bansard , Céline Bouclier , Béatrice Chabi , François Casas , Ornella Clara , Béatrice Bonafos , Xavier Mialhe , Chantal Cazevieille , Szimonetta Hideg , Armelle Choquet , Amandine Bastide , Julie Pannequin , Maria Duca , Alexandre David","doi":"10.1016/j.chembiol.2025.03.008","DOIUrl":"10.1016/j.chembiol.2025.03.008","url":null,"abstract":"<div><div>Tumor initiating cells (TICs) are the roots of current shortcomings in advanced and metastatic cancer treatment. Endowed with self-renewal and multi-lineage differentiation capacity, TICs can disseminate and seed metastasis in distant organ. Our work identified streptomycin (SM), a potent bactericidal antibiotic, as a molecule capable of specifically targeting non-adherent TIC from colon and breast cancer cell lines. SM induces iron-dependent, reactive oxygen species (ROS)-mediated cell death, which is mechanistically distinct from RSL3-induced ferroptosis. SM-induced cell death is associated with profound alterations in mitochondrial morphology. This effect results from COX1 inhibition, which disrupts the regulation of the cytochrome <em>c</em> oxidase complex and triggers mitochondrial ROS production. SM’s aldehyde group is essential, as its reduction into dihydrostreptomycin (DSM) abolishes its activity. These findings reveal a mechanism of action for streptomycin, shedding light on TIC metabolism and resistance, with potential implications for advanced cancer treatment.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 4","pages":"Pages 570-585.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806305","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