Cell Chemical Biology最新文献

Charting the development and engineering of CRISPR base editors: lessons and inspirations 绘制CRISPR碱基编辑器的发展和工程：教训和启示

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-06-05 DOI: 10.1016/j.chembiol.2025.05.003

Siyuan Zou, Yihong Sun, Weixin Tang

引用次数: 0

Mechanism by which the molecular glue-like verteporfin induces IRE1α dimerization and activation to synergize with AKT inhibition in breast cancer 分子胶样维替波芬诱导乳腺癌中IRE1α二聚化和活化协同抑制AKT的机制

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-06-04 DOI: 10.1016/j.chembiol.2025.05.004

Yongliang Liu, Hui Hua, Yalan Cao, Minjing Li, Hongying Zhang, Shan Du, Jieya Liu, Ting Luo, Yangfu Jiang

{"title":"Mechanism by which the molecular glue-like verteporfin induces IRE1α dimerization and activation to synergize with AKT inhibition in breast cancer","authors":"Yongliang Liu, Hui Hua, Yalan Cao, Minjing Li, Hongying Zhang, Shan Du, Jieya Liu, Ting Luo, Yangfu Jiang","doi":"10.1016/j.chembiol.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.chembiol.2025.05.004","url":null,"abstract":"Inositol-requiring enzyme 1α (IRE1α) signaling is one of three arms of the unfolded protein response, playing a vital role in maintaining endoplasmic reticulum homeostasis. Pharmacological modulation of this pathway offers potential therapeutic strategies for various diseases. Molecular glues may regulate protein stability and activity by inducing protein-protein interaction. Here, we find that verteporfin functions as a molecular glue, promoting IRE1α dimerization and activation. Specifically, verteporfin binds to IRE1α, facilitating its dimerization, which relies on the His692 residue. This activation of IRE1α triggers XBP1 splicing and miR-153-mediated downregulation of PTEN, along with AKT phosphorylation. Additionally, we identify the pro-metastasis gene <em>BACH1</em> as a novel target of miR-153, which is downregulated by IRE1α and verteporfin. While verteporfin inhibits breast cancer cell viability and invasion, its combination with an AKT inhibitor synergistically suppresses breast cancer progression. Our findings establish a mechanistic link between IRE1α and PI3K/AKT signaling, highlighting a possibility for therapeutic intervention.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"70 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211168","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

Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma 用于裂口边缘和体周谷氨酸同时检测的电化学传感器工具箱

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-06-03 DOI: 10.1016/j.chembiol.2025.05.002

Jie Liu, Yuandong Liu, Dongmin Yin, Yang Tian

引用次数: 0

The critical role of PSAC channel in malaria parasite survival is driven home by phenotypic screening under relevant nutrient levels PSAC通道在疟疾寄生虫存活中的关键作用是通过相关营养水平下的表型筛选来实现的

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-23 DOI: 10.1016/j.chembiol.2025.05.001

Irene Molina, Ryan Mansell, Rui Liang, Benigno Crespo, Margarita Puente, Virginia Franco, Sara Viera, Isabel Camino, Anas Saadeddin, Peter Bellotti, Annie Leung, Sam Henning, Shan Sun, Mikayla Herring, Celia Lopez, Carmen Cuevas, Peter Pogány, Beatriz Urones, Leigh Baxt, Esther Fernández, Lydia Mata-Cantero

{"title":"The critical role of PSAC channel in malaria parasite survival is driven home by phenotypic screening under relevant nutrient levels","authors":"Irene Molina, Ryan Mansell, Rui Liang, Benigno Crespo, Margarita Puente, Virginia Franco, Sara Viera, Isabel Camino, Anas Saadeddin, Peter Bellotti, Annie Leung, Sam Henning, Shan Sun, Mikayla Herring, Celia Lopez, Carmen Cuevas, Peter Pogány, Beatriz Urones, Leigh Baxt, Esther Fernández, Lydia Mata-Cantero","doi":"10.1016/j.chembiol.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.chembiol.2025.05.001","url":null,"abstract":"Spreading resistance to front-line treatments necessitate the search for new classes of antimalarials. Limitations of standard screening conditions lead us to develop an assay using culture media that more closely reflects nutrient levels in human serum to reveal new therapeutically relevant parasite pathways. Our approach was validated by testing 22k compounds followed by a full 750k compound screen and identified 29 chemotypes with higher activity in nutrient restricted media that were further characterized. Through a combination of chemo-genomics and innovative photocatalytic proximity labeling proteomics, we identified the target of two compounds as the CLAG3 component of the plasmodial surface anion channel (PSAC). Strikingly, every one of the other 29 chemotypes selected was also found to block PSAC activity, highlighting the importance of this nutrient channel for parasite survival under physiological conditions. The effect of PSAC inhibitors in the <em>in vivo</em> humanized mouse model was confirmed.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"45 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122572","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

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 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-05-15 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":"10.1016/j.chembiol.2025.04.004","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 5","pages":"Pages 736-751.e8"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","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 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