EMBO Reports最新文献_第7页

Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts. 线粒体周围肌动蛋白丝通过破坏er -线粒体接触抑制Parkin组装。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-29 DOI: 10.1038/s44319-025-00561-y

Tak Shun Fung, Amrapali Ghosh, Maite R Zavala, Zuzana Nichtova, Dhavalkumar Shukal, Marco Tigano, Gyorgy Csordas, Henry N Higgs, Rajarshi Chakrabarti

{"title":"Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts.","authors":"Tak Shun Fung, Amrapali Ghosh, Maite R Zavala, Zuzana Nichtova, Dhavalkumar Shukal, Marco Tigano, Gyorgy Csordas, Henry N Higgs, Rajarshi Chakrabarti","doi":"10.1038/s44319-025-00561-y","DOIUrl":"https://doi.org/10.1038/s44319-025-00561-y","url":null,"abstract":"Mitochondrial damage represents a dramatic change in cellular homeostasis, necessitating metabolic adaptation and clearance of the damaged organelle. One rapid response to mitochondrial damage is peri-mitochondrial actin polymerization within 2 min, which we term ADA (Acute Damage-induced Actin). ADA is vital for a metabolic shift from oxidative phosphorylation to glycolysis upon mitochondrial dysfunction. In the current study, we investigated the effect of ADA on Pink1/Parkin mediated mitochondrial quality control. We show that inhibition of proteins involved in the ADA pathway significantly accelerates Parkin recruitment onto depolarized mitochondria. Addressing the mechanism by which ADA resists Parkin recruitment onto depolarized mitochondria, we found that ADA disrupts ER-mitochondria contacts in an Arp2/3 complex-dependent manner. Interestingly, overexpression of ER-mitochondria tethers overrides the effect of ADA, allowing rapid recruitment of not only Parkin but also LC3 after mitochondrial depolarization. During chronic mitochondrial dysfunction, Parkin and LC3 recruitment are completely blocked, which is reversed rapidly by inhibiting ADA. Taken together we show that ADA acts as a protective mechanism, delaying mitophagy following acute damage, and blocking mitophagy during chronic mitochondrial damage.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947014","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

Direct visualization of HIV-1 core nuclear import and its interplay with the nuclear pore. 直接可视化HIV-1核心核输入及其与核孔的相互作用。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-29 DOI: 10.1038/s44319-025-00567-6

Zhen Hou, Stanley Fronik, Yao Shen, Long Chen, Christopher Thompson, Sarah Neumann, Peijun Zhang

{"title":"Direct visualization of HIV-1 core nuclear import and its interplay with the nuclear pore.","authors":"Zhen Hou, Stanley Fronik, Yao Shen, Long Chen, Christopher Thompson, Sarah Neumann, Peijun Zhang","doi":"10.1038/s44319-025-00567-6","DOIUrl":"https://doi.org/10.1038/s44319-025-00567-6","url":null,"abstract":"Direct visualization of HIV-1 nuclear import through the nuclear pore complex (NPC) presents a technical challenge due to the rarity of this process. To enable systematic investigation, we developed a robust in situ system that mimics HIV-1 nuclear import in a near-native context using isolated HIV-1 virus like particles (VLP) cores and permeabilized CD4 + T lymphocyte (CEM) cells. This approach supports docking and translocation of abundant viral cores through nuclear pores into the nucleus. For high-resolution visualization, we implemented an integrated correlative approach to guide cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) imaging, enabling precise targeting and structural characterization of individual nuclear import events. Using this workflow, we visualized 510 HIV-1 VLP cores at distinct stages of nuclear import, capturing key snapshots of the full progression of nuclear import. Subsequent statistical and structural analyses allow classification of core morphologies and identification of translocation-associated remodeling in nuclear pores. This work provides a methodological foundation for dissecting HIV-1 and potentially other viruses nuclear import processes and post-entry events in a controlled and quantitative manner.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947021","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

Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control. Nrm1是连接细胞周期进程和转录控制的双稳态开关。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-29 DOI: 10.1038/s44319-025-00566-7

Guillem Murciano-Julià, Montserrat Vega, Esther Pazo, Àlex Pascual-Serra, Isabel Alves-Rodrigues, Oriol Bagudanch, Roger Anglada, Núria Bonet, Rosa Aligué, Sergio Moreno, Baldo Oliva, Elena Hidalgo, José Ayté

{"title":"Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control.","authors":"Guillem Murciano-Julià, Montserrat Vega, Esther Pazo, Àlex Pascual-Serra, Isabel Alves-Rodrigues, Oriol Bagudanch, Roger Anglada, Núria Bonet, Rosa Aligué, Sergio Moreno, Baldo Oliva, Elena Hidalgo, José Ayté","doi":"10.1038/s44319-025-00566-7","DOIUrl":"https://doi.org/10.1038/s44319-025-00566-7","url":null,"abstract":"Entry into the cell cycle requires activation of G1 cyclin-dependent kinases (CDKs) and the G1/S transcriptional program. In fission yeast, the MBF complex is the main transcription factor driving early cell-cycle gene expression. MBF-dependent transcription is activated in metaphase and repressed at the end of S phase by a feedback loop involving the cyclin Cig2 and co-repressors Nrm1 and Yox1. While replicative stress inactivates Yox1 via phosphorylation, the mechanism that activates MBF during an unperturbed cell cycle remains unclear. Here, we identify Nrm1 as the key target of cell cycle regulation in a two-step control mechanism. First, CDK1 phosphorylates Nrm1 in metaphase, leading to its release-along with Yox1-from chromatin. Second, unphosphorylated Nrm1, generated either by dephosphorylation or de novo synthesis, is degraded during anaphase, preventing its re-association with MBF until the end of the next S phase. Together, these parallel pathways create a precisely timed window of MBF activation, ensuring proper cell cycle progression and preserving genomic stability.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947019","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

STAT3 sustains tumorigenicity following mutant KRAS ablation. 突变KRAS消融后STAT3维持致瘤性。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-26 DOI: 10.1038/s44319-025-00563-w

Stephen D'Amico, Varvara Kirillov, Jingxuan Liu, Zhijuan Qiu, Xinyuan Lei, Hong Qin, Brian S Sheridan, Nancy C Reich

{"title":"STAT3 sustains tumorigenicity following mutant KRAS ablation.","authors":"Stephen D'Amico, Varvara Kirillov, Jingxuan Liu, Zhijuan Qiu, Xinyuan Lei, Hong Qin, Brian S Sheridan, Nancy C Reich","doi":"10.1038/s44319-025-00563-w","DOIUrl":"10.1038/s44319-025-00563-w","url":null,"abstract":"Oncogenic KRAS mutations underlie some of the deadliest human cancers. Genetic or pharmacological KRAS inactivation produces mixed outcomes and frequent relapse. Mechanisms of tumor resistance to KRAS inhibition remain poorly understood. We present evidence that STAT3 supports tumor growth following KRAS depletion. Using a conceptual framework of pancreatic ductal adenocarcinoma, we show that cancer cells that survive CRISPR-mediated ablation of mutant KRAS are dependent on STAT3 function to maintain tumorigenicity. Mechanistically, the combined loss of mutant KRAS and STAT3 disrupts a core transcriptional program of cancer cells critical to oncogenic competence. This in turn impairs tumor growth in mice and enhances immune rejection, leading to tumor clearance. We propose that the STAT3 transcriptional program operating in cancer cells enforces their malignant identity, rather than providing classical features of transformation, and shapes cancer persistence following KRAS inactivation. Our findings establish STAT3 as a critical enforcer of oncogenic identity in KRAS-ablated tumors, revealing a key vulnerability.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947039","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

PCAF-mediated acetylation regulates RAD51 dynamic localization on chromatin during HR repair. 在HR修复过程中，pcaf介导的乙酰化调节RAD51在染色质上的动态定位。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-15 DOI: 10.1038/s44319-025-00513-6

Jiajia Hou, Munan Shi, Jialu Hong, Yuting Liu, Xinyi Song, Haipeng Rao, Ying Ma, Chunchun Huang, Zhigang Hu, Lingfeng He, Zhigang Guo, Feiyan Pan

{"title":"PCAF-mediated acetylation regulates RAD51 dynamic localization on chromatin during HR repair.","authors":"Jiajia Hou, Munan Shi, Jialu Hong, Yuting Liu, Xinyi Song, Haipeng Rao, Ying Ma, Chunchun Huang, Zhigang Hu, Lingfeng He, Zhigang Guo, Feiyan Pan","doi":"10.1038/s44319-025-00513-6","DOIUrl":"10.1038/s44319-025-00513-6","url":null,"abstract":"PCAF (p300-associated factor), a major histone acetyltransferase, is involved in many metabolic and pathogenic diseases. Here, we reveal a novel function of PCAF in homologous recombination repair (HR). We demonstrate that RAD51, a core protein in HR repair, physically interacts with the acetyltransferase domain of PCAF and is acetylated at lysine 40. This acetylation promotes RAD51 binding to ubiquitin, leading to its degradation via the ubiquitin-proteasome pathway. Following etoposide treatment, PCAF-induced acetylation removes RAD51 from chromatin to facilitate the late-phase HR processes. Overexpression of PCAF promotes premature dissociation of RAD51 from DNA damage sites. Notably, PCAF is downregulated in many cancers compared to adjacent tissues, correlating with shortened patient survival. Our findings suggest that decreased PCAF expression enhances HR efficiency, contributing to drug resistance in tumor cells, and the impact of PCAF on HR is dependent on its acetyltransferase activity. Our results highlight a novel role of PCAF in HR and provide a possible mechanism for tumor development and drug resistance caused by low expression of PCAF.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4100-4123"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642097","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

Food for thought : Perspectives on the current state of Vertical Farming. 思考的食物：对垂直农业现状的看法。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-21 DOI: 10.1038/s44319-025-00518-1

Jeremy Harbinson, Craig R Taylor

引用次数: 0

A genetic framework for RNAi inheritance in Caenorhabditis elegans. 秀丽隐杆线虫RNAi遗传的遗传框架。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-07 DOI: 10.1038/s44319-025-00512-7

Jan Schreier, Lizaveta Pshanichnaya, Fridolin Kielisch, René F Ketting

{"title":"A genetic framework for RNAi inheritance in Caenorhabditis elegans.","authors":"Jan Schreier, Lizaveta Pshanichnaya, Fridolin Kielisch, René F Ketting","doi":"10.1038/s44319-025-00512-7","DOIUrl":"10.1038/s44319-025-00512-7","url":null,"abstract":"Gene regulation by RNA interference (RNAi) is a conserved process driven by double-stranded RNA (dsRNA). It responds to exogenous cues and drives endogenous gene regulation. In Caenorhabditis elegans, RNAi can be inherited from parents to offspring. While a number of factors have been implicated in this inheritance process, we do not understand how and when they function. Using a new inheritance assay, we establish a hierarchy amongst previously identified inheritance factors. We show that the nuclear Argonaute protein HRDE-1 is required for RNAi establishment in parents and offspring, but not for the inheritance process. In contrast, the cytoplasmic Argonaute protein WAGO-3 is the only factor essential for inheritance, via sperm and oocyte, while not affecting establishment in either parent or offspring. We propose a cycle in which nuclear and cytoplasmic Argonaute proteins interact to generate both a silencing response and a cytoplasmic factor that transmits the silencing between parent and offspring, WAGO-3. Finally, we implicate the RNA helicase ZNFX-1 as a factor that allows the inherited WAGO-3 protein to trigger silencing in the offspring.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4072-4099"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583382","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

GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation. GPNMB标志着黑色素瘤中的静止细胞群并促进转移形成。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-06-17 DOI: 10.1038/s44319-025-00501-w

Fiorenza Lotti, Marine Melixetian, Thalia Vlachou, Marco S Nobile, Leone Bacciu, Marco Malferrari, Nicolò Quaresima, Stefania Rapino, Federica Marocchi, Massimo Barberis, Chiara Soriani, Barbara Gallo, Velia Mollo, Ilaria Ferrarotto, Daniela Bossi, Pier Francesco Ferrucci, Pier Giuseppe Pelicci, Lucilla Luzi, Luisa Lanfrancone

{"title":"GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation.","authors":"Fiorenza Lotti, Marine Melixetian, Thalia Vlachou, Marco S Nobile, Leone Bacciu, Marco Malferrari, Nicolò Quaresima, Stefania Rapino, Federica Marocchi, Massimo Barberis, Chiara Soriani, Barbara Gallo, Velia Mollo, Ilaria Ferrarotto, Daniela Bossi, Pier Francesco Ferrucci, Pier Giuseppe Pelicci, Lucilla Luzi, Luisa Lanfrancone","doi":"10.1038/s44319-025-00501-w","DOIUrl":"10.1038/s44319-025-00501-w","url":null,"abstract":"Melanoma exhibits high intratumoral heterogeneity, characterized by a diverse population of cells undergoing dynamic transitions between cellular states. These adaptive changes enable melanoma cells to survive in the harsh tumor microenvironment, acquire drug resistance, and metastasize. One such state, quiescence, has been linked to both relapse and drug resistance, but its underlying biology and molecular mechanisms remain poorly understood. Our study challenges the conventional understanding of melanoma quiescence. Contrary to the notion of a rare, unique subpopulation, we demonstrate that quiescence is a highly dynamic state accessible to most, if not all, melanoma cells. This state is exquisitely sensitive to microenvironmental cues. We identify GPNMB as a marker of quiescence, that is expressed in both primary and metastatic tumors. GPNMB-positive cells exhibit a pro-metastatic phenotype and are enriched in metastatic sites, suggesting a potential role for quiescence in tumor dissemination. Our findings position GPNMB as a valuable marker for isolating quiescent melanoma cells and as a potential therapeutic target to tackle metastasis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3804-3830"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316204","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

Targeted protein degradation in Escherichia coli using CLIPPERs. 利用CLIPPERs对大肠杆菌进行靶向蛋白降解。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-06-25 DOI: 10.1038/s44319-025-00510-9

Matylda Anna Izert-Nowakowska, Maria Magdalena Klimecka, Anna Antosiewicz, Karol Wróblewski, Jakub Józef Kowalski, Katarzyna Justyna Bandyra, Tomasz Góral, Sebastian Kmiecik, Remigiusz Adam Serwa, Maria Wiktoria Górna

{"title":"Targeted protein degradation in Escherichia coli using CLIPPERs.","authors":"Matylda Anna Izert-Nowakowska, Maria Magdalena Klimecka, Anna Antosiewicz, Karol Wróblewski, Jakub Józef Kowalski, Katarzyna Justyna Bandyra, Tomasz Góral, Sebastian Kmiecik, Remigiusz Adam Serwa, Maria Wiktoria Górna","doi":"10.1038/s44319-025-00510-9","DOIUrl":"10.1038/s44319-025-00510-9","url":null,"abstract":"New, universal tools for targeted protein degradation in bacteria can help to accelerate protein function studies and antimicrobial research. We describe a new method for degrading bacterial proteins using plasmid-encoded degrader peptides which deliver target proteins for degradation by a highly conserved ClpXP protease. We demonstrate the mode of action of the degraders on a challenging essential target, GroEL. The studies in bacteria are complemented by in vitro binding and structural studies. Expression of degrader peptides results in a temperature-dependent growth inhibition and depletion of GroEL levels over time. The reduction of GroEL levels is accompanied by dramatic proteome alterations. The presented method offers a new alternative approach for regulating protein levels in bacteria without genomic modifications or tag fusions. Our studies demonstrate that ClpXP is an attractive protease for the future use in bacterial-targeted protein degradation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3994-4016"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495219","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

Machines like us scientists? : AI tools for mining the scientific literature in basic biomedical science. 像我们科学家一样的机器？：用于基础生物医学科学科学文献挖掘的AI工具。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-10 DOI: 10.1038/s44319-025-00522-5

Blanche Schwappach

引用次数: 0