Cell Chemical Biology最新文献_第3页

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 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 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":"10.1016/j.chembiol.2025.04.003","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 5","pages":"Pages 752-766.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","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

Spatiotemporally resolved GPCR interactome uncovers unique mediators of receptor agonism 时空分辨的GPCR相互作用揭示了受体激动作用的独特介质

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.006

Maria M. Shchepinova , Rachel Richardson , Jack W. Houghton , Abigail R. Walker , Mohammed A. Safar , Daniel Conole , Aylin C. Hanyaloglu , Edward W. Tate

{"title":"Spatiotemporally resolved GPCR interactome uncovers unique mediators of receptor agonism","authors":"Maria M. Shchepinova , Rachel Richardson , Jack W. Houghton , Abigail R. Walker , Mohammed A. Safar , Daniel Conole , Aylin C. Hanyaloglu , Edward W. Tate","doi":"10.1016/j.chembiol.2025.04.006","DOIUrl":"10.1016/j.chembiol.2025.04.006","url":null,"abstract":"<div><div>Cellular signaling by membrane G protein-coupled receptors (GPCRs) is governed by a complex and diverse array of mechanisms. The dynamics of a GPCR interactome, as it evolves over time and space in response to an agonist, provide a unique perspective on pleiotropic signaling decoding and functional selectivity at the cellular level. In this study, we utilized proximity-based APEX2 proteomics to investigate the interaction network of the luteinizing hormone receptor (LHR) on a minute-to-minute timescale. We developed an analytical approach that integrates quantitative multiplexed proteomics with temporal reference profiles, creating a platform to identify the proteomic environment of APEX2-tagged LHR at the nanometer scale. LHR activity is finely regulated spatially, leading to the identification of putative interactors, including the Ras-related GTPase RAP2B, which modulate both receptor signaling and post-endocytic trafficking. This work provides a valuable resource for spatiotemporal nanodomain mapping of LHR interactors across subcellular compartments.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 5","pages":"Pages 722-735.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948966","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

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

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.005

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

引用次数: 0

Meet the Cell Chemical Biology author and newest advisory board member: Marcus Conrad 认识一下《细胞化学生物学》的作者和最新的顾问委员会成员：马库斯·康拉德

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.011

Marcus Conrad

引用次数: 0

Meet the authors: Xing Zhang, Kyong Fam, Tingting Dai, and Howard Hang 见见作者：张星、法京、戴婷婷和杭霍华德

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.010

Xing Zhang, Kyong Fam, Tingting Dai, Howard Hang

引用次数: 0

Engineering ERα degraders with pleiotropic ubiquitin ligase ligands maximizes therapeutic efficacy by co-opting distinct effector ligases 工程ERα降解剂与多效泛素连接酶配体通过选择不同的效应连接酶最大限度地提高治疗效果

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.008

Anna Shemorry , Willem den Besten , Melinda M. Mulvihill , Curt J. Essenburg , Nicole Blaquiere , Tracy Kleinheinz , Elisia Villemure , Frank Peale , Gauri Deshmukh , Danilo Maddalo , Elizabeth Levy , Kebing Yu , Matthew R. Steensma , Elizabeth A. Tovar , Emily Wolfrum , Karthik Nagapudi , Robert A. Blake , William F. Forrest , Steven T. Staben , Carrie R. Graveel , Ingrid E. Wertz

{"title":"Engineering ERα degraders with pleiotropic ubiquitin ligase ligands maximizes therapeutic efficacy by co-opting distinct effector ligases","authors":"Anna Shemorry , Willem den Besten , Melinda M. Mulvihill , Curt J. Essenburg , Nicole Blaquiere , Tracy Kleinheinz , Elisia Villemure , Frank Peale , Gauri Deshmukh , Danilo Maddalo , Elizabeth Levy , Kebing Yu , Matthew R. Steensma , Elizabeth A. Tovar , Emily Wolfrum , Karthik Nagapudi , Robert A. Blake , William F. Forrest , Steven T. Staben , Carrie R. Graveel , Ingrid E. Wertz","doi":"10.1016/j.chembiol.2025.04.008","DOIUrl":"10.1016/j.chembiol.2025.04.008","url":null,"abstract":"<div><div>Proximity-inducing compounds that modulate target protein homeostasis represent an emerging therapeutic strategy. While the inherent complexity of these bifunctional compounds presents certain challenges, their unique composition offers opportunities to co-opt specific cellular effectors to enhance therapeutic impact. In this study, we systematically evaluate a series of bifunctional degrader compounds engineered with the estrogen receptor-alpha (ERα) inhibitor endoxifen linked to various bioactive ubiquitin ligase ligands. Notably, ERα degraders containing pan-IAP antagonist ligands significantly reduced the proliferation of ERα-dependent cells compared to clinical-stage ERα degraders. These pan-IAP antagonist-based ERα degraders leverage distinct effector ligases to achieve dual therapeutic effects: They utilize XIAP within tumor cells to promote ERα degradation and activate cIAP1/2 in both tumor and immune cells to induce TNFα, which drives tumor cell death. Our findings illustrate a broader concept that co-opting the discrete functions of selected cellular effectors, while simultaneously modulating therapeutic target protein homeostasis, are dual strategies that can significantly enhance the efficacy of induced proximity therapeutics.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 5","pages":"Pages 694-709.e35"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948964","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 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.002

Jiashuo Zheng (郑嘉烁) , Weijia Zhang (张唯佳) , Junya Ito , Bernhard Henkelmann , Chenxi Xu (徐晨曦) , Eikan Mishima , Marcus Conrad

{"title":"N-acetyl-l-cysteine averts ferroptosis by fostering glutathione peroxidase 4","authors":"Jiashuo Zheng (郑嘉烁) , Weijia Zhang (张唯佳) , Junya Ito , Bernhard Henkelmann , Chenxi Xu (徐晨曦) , Eikan Mishima , Marcus Conrad","doi":"10.1016/j.chembiol.2025.04.002","DOIUrl":"10.1016/j.chembiol.2025.04.002","url":null,"abstract":"<div><div><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.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 5","pages":"Pages 767-775.e5"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","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

Decoding the minute-by-minute GPCR interactome unveils hormone signaling gatekeepers 解码每分钟的GPCR相互作用组揭示激素信号的守门人

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.012

Wenqing Shui

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 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 DOI: 10.1016/j.chembiol.2025.04.001

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

引用次数: 0

Meet the authors: Mitchel L. Tepe and Huiqing Zhou 认识一下作者：mitchell L. Tepe和Huiqing Zhou