Nature chemical biology最新文献_第2页

REPLACE-ing RNA through evolution

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-02-04 DOI: 10.1038/s41589-025-01845-z

Christopher E. Denes, G. Gregory Neely

引用次数: 0

ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-29 DOI: 10.1038/s41589-024-01825-9

Lei Wang, Runze Shi, Shuo Wang, Yuran Duan, Zheng Wang, Peixiang Zheng, Xue Sun, Xiaohan Chen, Guimei Ji, Yuli Shen, Bofei Dong, Yanni Lin, Ting Wen, Qi Tian, Zhanpeng Guo, Yueru Hou, Shiqi Wu, Ling Xiao, Min Li, Liwei Xiao, Qingang Wu, Ying Meng, Guijun Liu, Sofie Duan, Xueli Bai, Tong Liu, Zhiren Zhang, Peng Zhan, Zhimin Lu, Daqian Xu

{"title":"ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation","authors":"Lei Wang, Runze Shi, Shuo Wang, Yuran Duan, Zheng Wang, Peixiang Zheng, Xue Sun, Xiaohan Chen, Guimei Ji, Yuli Shen, Bofei Dong, Yanni Lin, Ting Wen, Qi Tian, Zhanpeng Guo, Yueru Hou, Shiqi Wu, Ling Xiao, Min Li, Liwei Xiao, Qingang Wu, Ying Meng, Guijun Liu, Sofie Duan, Xueli Bai, Tong Liu, Zhiren Zhang, Peng Zhan, Zhimin Lu, Daqian Xu","doi":"10.1038/s41589-024-01825-9","DOIUrl":"https://doi.org/10.1038/s41589-024-01825-9","url":null,"abstract":"As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1. Beclin1-associated ADSL produces fumarate, which in turn inhibits lysine demethylase 8-mediated Beclin1 demethylation, resulting in enhanced Beclin1 K117me2, subsequent disruption of the binding of BCL-2 to Beclin1 and elevated autophagy. Blocking the ADSL–Beclin1 axis by knock-in mutation or a cell-penetrating peptide inhibits autophagy induced by lipid deprivation and ER stress and blunts liver tumor growth in mice. Additionally, ADSL pS140-upregulated Beclin1 K117me2 levels are positively correlated with autophagy levels in human hepatocellular carcinoma specimens and poor patient prognosis. These findings uncover the function of ADSL in autophagy regulation and liver tumor development.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"7 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055014","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

Quinone extraction drives atmospheric carbon monoxide oxidation in bacteria

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-29 DOI: 10.1038/s41589-025-01836-0

Ashleigh Kropp, David L. Gillett, Hari Venugopal, Miguel A. Gonzálvez, James P. Lingford, Surbhi Jain, Christopher K. Barlow, Jie Zhang, Chris Greening, Rhys Grinter

{"title":"Quinone extraction drives atmospheric carbon monoxide oxidation in bacteria","authors":"Ashleigh Kropp, David L. Gillett, Hari Venugopal, Miguel A. Gonzálvez, James P. Lingford, Surbhi Jain, Christopher K. Barlow, Jie Zhang, Chris Greening, Rhys Grinter","doi":"10.1038/s41589-025-01836-0","DOIUrl":"https://doi.org/10.1038/s41589-025-01836-0","url":null,"abstract":"Diverse bacteria and archaea use atmospheric CO as an energy source for long-term survival. Bacteria use [MoCu]-CO dehydrogenases (Mo-CODH) to convert atmospheric CO to carbon dioxide, transferring the obtained electrons to the aerobic respiratory chain. However, it is unknown how these enzymes oxidize CO at low concentrations and interact with the respiratory chain. Here, we use cryo-electron microscopy and structural modeling to show how Mo-CODHMs (CoxSML) from Mycobacterium smegmatis interacts with its partner, the membrane-bound menaquinone-binding protein CoxG. We provide electrochemical, biochemical and genetic evidence that Mo-CODH transfers CO-derived electrons to the aerobic respiratory chain through CoxG. Lastly, we show that Mo-CODH and CoxG genetically and structurally associate in diverse bacteria and archaea. These findings reveal the basis of the biogeochemically and ecologically important process of atmospheric CO oxidation, while demonstrating that long-range quinone transport is a general mechanism of energy conservation, which convergently evolved on multiple occasions.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"52 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054911","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

Mechanistic insights and approaches for beta cell regeneration

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-29 DOI: 10.1038/s41589-024-01822-y

Christos Karampelias, Ka-Cheuk Liu, Anders Tengholm, Olov Andersson

{"title":"Mechanistic insights and approaches for beta cell regeneration","authors":"Christos Karampelias, Ka-Cheuk Liu, Anders Tengholm, Olov Andersson","doi":"10.1038/s41589-024-01822-y","DOIUrl":"https://doi.org/10.1038/s41589-024-01822-y","url":null,"abstract":"Diabetes is characterized by variable loss of insulin-producing beta cells, and new regenerative approaches to increasing the functional beta cell mass of patients hold promise for reversing disease progression. In this Review, we summarize recent chemical biology breakthroughs advancing our knowledge of beta cell regeneration. We present current chemical-based tools, sensors and mechanistic insights into pathways that can be targeted to enhance beta cell regeneration in model organisms. We group the pathways according to the cellular processes they affect, that is, proliferation, conversion of other mature cell types to beta cells and beta cell differentiation from progenitor-like populations. We also suggest assays for assessing the functionality of the regenerated beta cells. Although regeneration processes differ between animal models, such as zebrafish, mice and pigs, regenerative mechanisms identified in any one animal model may be translatable to humans. Overall, chemical biology-based approaches in beta cell regeneration give hope that specific molecular pathways can be targeted to enhance beta cell regeneration.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"9 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055013","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

How to build a [2Fe–2S] cluster 如何构建 [2Fe-2S] 簇

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-28 DOI: 10.1038/s41589-024-01835-7

Anna Moseler, Stephan Wagner, Andreas J. Meyer

引用次数: 0

The measurement, regulation and biological activity of FAHFAs

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-28 DOI: 10.1038/s41589-024-01827-7

Dan Tan, Alan Saghatelian

引用次数: 0

Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-27 DOI: 10.1038/s41589-024-01826-8

Wen Li, Xiaoxian Shi, Caiwei Tan, Zhaodi Jiang, Mingyi Li, Zhiheng Ji, Jing Zhou, Mengxin Luo, Zuyan Fan, Zhifan Ding, Yue Fang, Jun Sun, Junjun Ding, Huasong Lu, Weirui Ma, Wei Xie, Wenjing Su

{"title":"Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance","authors":"Wen Li, Xiaoxian Shi, Caiwei Tan, Zhaodi Jiang, Mingyi Li, Zhiheng Ji, Jing Zhou, Mengxin Luo, Zuyan Fan, Zhifan Ding, Yue Fang, Jun Sun, Junjun Ding, Huasong Lu, Weirui Ma, Wei Xie, Wenjing Su","doi":"10.1038/s41589-024-01826-8","DOIUrl":"https://doi.org/10.1038/s41589-024-01826-8","url":null,"abstract":"RAF protein kinases are major RAS effectors that function by phosphorylating MEK. Although all three RAF isoforms share a conserved RAS binding domain and bind to GTP-loaded RAS, only ARAF uniquely enhances RAS activity. Here we uncovered the molecular basis of ARAF in regulating RAS activation. The disordered N-terminal sequence of ARAF drives self-assembly, forming ARAF–RAS condensates tethered to the plasma membrane. These structures concentrate active RAS locally, impeding NF1-mediated negative regulation of RAS, thereby fostering receptor tyrosine kinase (RTK)-triggered RAS activation. In RAS-mutant tumors, loss of the ARAF N terminus sensitizes tumor cells to pan-RAF inhibition. In hormone-sensitive cancers, increased ARAF condensates drive endocrine therapy resistance, whereas ARAF depletion reverses RTK-dependent resistance. Our findings delineate ARAF–RAS protein condensates as distinct subcellular structures sustaining RAS activity and facilitating oncogenic RAS signaling. Targeting ARAF–RAS condensation may offer a strategy to overcome drug resistance in both wild-type and mutant ARAF-mediated scenarios.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044126","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 ISC machinery assembles [2Fe–2S] clusters by formation and fusion of [1Fe–1S] precursors

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-27 DOI: 10.1038/s41589-024-01818-8

Sylvain Gervason, Rafal Dutkiewicz, Kristian Want, Rania Benazza, Rémi Mor-Gautier, Aneta Grabinska-Rogala, Christina Sizun, Oscar Hernandez-Alba, Sarah Cianferani, Bruno Guigliarelli, Bénédicte Burlat, Benoit D’Autréaux

{"title":"The ISC machinery assembles [2Fe–2S] clusters by formation and fusion of [1Fe–1S] precursors","authors":"Sylvain Gervason, Rafal Dutkiewicz, Kristian Want, Rania Benazza, Rémi Mor-Gautier, Aneta Grabinska-Rogala, Christina Sizun, Oscar Hernandez-Alba, Sarah Cianferani, Bruno Guigliarelli, Bénédicte Burlat, Benoit D’Autréaux","doi":"10.1038/s41589-024-01818-8","DOIUrl":"https://doi.org/10.1038/s41589-024-01818-8","url":null,"abstract":"Iron–sulfur clusters are essential metallocofactors synthesized by multiprotein machineries via an unclear multistep process. Here we report a step-by-step dissection of the [2Fe–2S] cluster assembly process by the Escherichia coli iron–sulfur cluster (ISC) assembly machinery using an in vitro reconstituted system and a combination of biochemical and spectroscopic techniques. We show that this process is initiated by iron binding to the scaffold protein IscU, which triggers persulfide insertion by the cysteine desulfurase IscS upon the formation of a complex with IscU. Then, the persulfide is cleaved into sulfide by the ferredoxin Fdx, leading to a [1Fe–1S] precursor. IscU dissociates from IscS, dimerizes and generates a bridging [2Fe–2S] cluster by fusion of two [1Fe–1S] precursors. The IscU dimer ultimately dissociates into a monomer, ready to transfer its [2Fe–2S] cluster to acceptors. These data provide a comprehensive description of the [2Fe–2S] cluster assembly process by the ISC assembly machinery, highlighting the formation of key intermediates through a tightly concerted process.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"4 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044125","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

Implications of frequent hitter E3 ligases in targeted protein degradation screens

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-01-27 DOI: 10.1038/s41589-024-01821-z

Xiaoyu Zhang, Gabriel M. Simon, Benjamin F. Cravatt

引用次数: 0

An influenza mutation switch 流感突变开关

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-01-23 DOI: 10.1038/s41589-025-01839-x

Francesco Zamberlan

引用次数: 0