EMBO Journal最新文献_第2页

GTPase Rab11b and effector Rab11-FIP2 promote NLRP3 stability during inflammasome priming. GTPase Rab11b和效应物Rab11-FIP2在炎症小体启动过程中促进NLRP3的稳定性。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-25 DOI: 10.1038/s44318-026-00755-7

Caroline S Gravastrand, Maria Yurchenko, Stine Kristensen, Astrid Skjesol, Carmen Chen, Sindre Ullmann, Zunaira Iqbal, Karoline Ruud Dahlen, Kashif Rasheed, Unni Nonstad, Liv Ryan, Terje Espevik, Harald Husebye

{"title":"GTPase Rab11b and effector Rab11-FIP2 promote NLRP3 stability during inflammasome priming.","authors":"Caroline S Gravastrand, Maria Yurchenko, Stine Kristensen, Astrid Skjesol, Carmen Chen, Sindre Ullmann, Zunaira Iqbal, Karoline Ruud Dahlen, Kashif Rasheed, Unni Nonstad, Liv Ryan, Terje Espevik, Harald Husebye","doi":"10.1038/s44318-026-00755-7","DOIUrl":"10.1038/s44318-026-00755-7","url":null,"abstract":"Membrane trafficking through the trans-Golgi network has been shown to guide activation of the NLRP3 inflammasome. Rab11 GTPases and their effector Rab11-FIP2 regulate endosomal trafficking and retrograde transport. Here, we demonstrate that Rab11b and Rab11-FIP2 contribute to NLRP3 and pro-IL-1β stabilization during the inflammasome priming phase, which is followed by inflammasome activation. We show Rab11-FIP2 to promote TAK1 phosphorylation and TAK1-mediated activation of IKKβ, a process controlling NLRP3 translocation to the trans-Golgi network. Human NLRP3 and Rab11-FIP2 bind each other via their phosphatidylinositol-4 phosphate (PI4P)-binding domains KMKK and N-terminal C2 domain, respectively. We also provide evidence indicating that Rab11-FIP2 stabilizes NLRP3 on early endosomes, which is important for ASC speck formation. These findings provide insights into the mechanisms controlling stability and intracellular trafficking of NLRP3 in human macrophages.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2991-3021"},"PeriodicalIF":8.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515937","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

Condensin loop extrusion properties, roadblocks, and role in homology search during recombination in S. cerevisiae. 浓缩蛋白环挤出特性、障碍及其在酿酒酵母重组过程中同源性搜索中的作用。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-23 DOI: 10.1038/s44318-026-00748-6

Vinciane Piveteau, Chloé Dupont, Hossein Salari, Agnès Dumont, Jérôme Savocco, Daniel Jost, Aurèle Piazza

{"title":"Condensin loop extrusion properties, roadblocks, and role in homology search during recombination in S. cerevisiae.","authors":"Vinciane Piveteau, Chloé Dupont, Hossein Salari, Agnès Dumont, Jérôme Savocco, Daniel Jost, Aurèle Piazza","doi":"10.1038/s44318-026-00748-6","DOIUrl":"10.1038/s44318-026-00748-6","url":null,"abstract":"The in vivo mechanism, cis-acting roadblocks, and biological functions of DNA loop extrusion by eukaryotic SMC complexes remain incompletely defined. Here, we identify condensin-dependent Hi-C contact stripes at the recombination enhancer (RE) and at rDNA in S. cerevisiae. The RE is an autonomous condensin loading site only active in MATa cells from which oriented, unidirectional loop extrusion proceeds with an estimated processivity ~150-250 kb and a density ~0.04-0.18 that varies across the cell cycle. Centromeres, replication forks, and highly transcribed RNA PolII-dependent genes represent roadblocks for condensin. Cohesin is not an obstacle for condensin, while Top2 promotes its loop extrusion activity. A DNA double-strand break (DSB) at MAT blocks loop extrusion, resulting in the establishment of a ~170 kb-long RE-MAT loop. The RE and the DSB are required and sufficient to form this site-specific loop, which promotes RE-proximal homology identification in the early stages of recombinational DNA break-repair. We propose that juxtaposition of the broken MATa site and its target HMLα donor is the relevant structure by which condensin promotes a-to-α mating-type switching.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3124-3155"},"PeriodicalIF":8.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505462","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

Ki-67 shapes the nucleolus by anchoring chromatin via its amphiphilic properties. Ki-67通过其两亲性特性锚定染色质形成核仁。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-24 DOI: 10.1038/s44318-026-00747-7

Daja Schichler, Yuki Hayashi, Letitia Fernandez, Mariam Chupanova, Alberto Hernandez-Armendariz, Beate Neumann, Sara Cuylen-Haering

{"title":"Ki-67 shapes the nucleolus by anchoring chromatin via its amphiphilic properties.","authors":"Daja Schichler, Yuki Hayashi, Letitia Fernandez, Mariam Chupanova, Alberto Hernandez-Armendariz, Beate Neumann, Sara Cuylen-Haering","doi":"10.1038/s44318-026-00747-7","DOIUrl":"10.1038/s44318-026-00747-7","url":null,"abstract":"The nucleolus, a membrane-less organelle essential for ribosome biogenesis, adopts variable shapes across cell types and in response to environmental conditions, yet the mechanisms regulating its morphology and functional implications remain unclear. Using a high-throughput screen, we identify the proliferation marker Ki-67 as a central regulator of nucleolar shape. Ki-67 localises to the chromatin-nucleolus interface, where its depletion induces nucleolar rounding and reduces chromatin enrichment both at the nucleolar rim and within internal invaginations. This effect is driven by Ki-67's amphiphilic properties conferred by two distinct affinity domains separated by a spacer. Given that chromatin loss is a common feature of rounded nucleoli in our screen, and acute chromatin digestion also induces rounding, we propose that the chromatin environment in and around the nucleolus plays a key role in determining nucleolar shape. Our study elucidates a novel Ki-67-mediated chromatin anchoring mechanism, tightly linking nucleolar shape to genome organisation and expanding our understanding of condensate morphology.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3156-3191"},"PeriodicalIF":8.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516009","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

The coordinated action of UFMylation and the RQC pathways clears arrested polypeptides at the ER. ufmyation和RQC通路的协同作用清除内质网中被阻滞的多肽。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-25 DOI: 10.1038/s44318-026-00753-9

Milica Mihailovic, Aleksandra S Anisimova, Bu Erte, Ni Zhan, Ioanna Styliara, Yasin Dagdas, Gülsün Elif Karagöz

{"title":"The coordinated action of UFMylation and the RQC pathways clears arrested polypeptides at the ER.","authors":"Milica Mihailovic, Aleksandra S Anisimova, Bu Erte, Ni Zhan, Ioanna Styliara, Yasin Dagdas, Gülsün Elif Karagöz","doi":"10.1038/s44318-026-00753-9","DOIUrl":"10.1038/s44318-026-00753-9","url":null,"abstract":"Clearance of arrested nascent polypeptides resulting from ribosomal stalling is essential for proteostasis. Stalled endoplasmic reticulum (ER)-bound ribosomes are marked by ubiquitin-fold modifier 1 (UFM1) on the large ribosomal subunit protein RPL26, but the precise role of this modification in ribosome-associated quality control (RQC) remains poorly understood. Here, we define the interplay between the UFMylation machinery and the RQC in clearing arrested polypeptides upon ribosome stalling at the ER. Proteomic analysis shows that RQC factors associate with UFMylated ribosomes. Functional assays demonstrate that ribosome rescue factors ZNF598 and ASC-1 recognize and split stalled ribosomes at the ER, a prerequisite for RPL26 UFMylation. The UFM1 E3 ligase complex then binds and UFMylates the post-split 60S-peptidyl-tRNA complex, facilitating access of RQC factors. Depletion of the NEMF/LTN1 complex leads to accumulation of UFMylated ribosomes, whereas impaired UFMylation weakens NEMF/LTN1 binding to ER-stalled ribosomes, supporting a physical link between these pathways. These findings demonstrate that RQC cooperates with the UFMylation machinery to overcome the topological constraints of clearing the arrested polypeptides at the ER.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3252-3275"},"PeriodicalIF":8.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516345","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

Microtubule end stabilisation by cooperative oligomers of Ska and Ndc80 complexes. Ska和Ndc80配合物寡聚物的微管末端稳定。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-20 DOI: 10.1038/s44318-026-00749-5

Renjith M Radhakrishnan, Lauren Stokes, Matthew Day, Pim J Huis In 't Veld, Vladimir A Volkov

{"title":"Microtubule end stabilisation by cooperative oligomers of Ska and Ndc80 complexes.","authors":"Renjith M Radhakrishnan, Lauren Stokes, Matthew Day, Pim J Huis In 't Veld, Vladimir A Volkov","doi":"10.1038/s44318-026-00749-5","DOIUrl":"10.1038/s44318-026-00749-5","url":null,"abstract":"During mitosis, properly aligned chromosomes stabilise microtubule ends with the help of kinetochores to ensure timely segregation of chromosomes. Microtubule-binding components of the human outer kinetochore, such as Ndc80 and Ska complexes, are present in multiple copies and together bind several microtubule ends, creating a highly multivalent binding interface. Whereas Ndc80:Ndc80 and Ndc80:microtubule binding is crucial for interface stability, Ndc80 alone in absence of Ska is unable to support stable kinetochore-attachments. Using cryo-electron tomography, we demonstrate that oligomeric Ndc80:Ska assemblies stabilise microtubule ends against shortening by strengthening lateral contacts between tubulin protofilaments at microtubule plus-ends. We further identify a point mutation within the SKA1 microtubule-binding domain that does not affect microtubule-binding of individual Ska molecules, but does abolish Ska:Ska interactions. Finally, we report that oligomerisation of Ska, in a cooperative fashion together with the Ndc80, is necessary to maintain stable microtubule attachments both in vivo and in vitro.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2905-2937"},"PeriodicalIF":8.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492077","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

FGF4 initiates X-chromosome inactivation via activating YY1 and prompting loss of pluripotency factors. FGF4通过激活YY1引发x染色体失活，并促使多能因子丢失。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-25 DOI: 10.1038/s44318-026-00722-2

Lizhu Ma, Wei Fu, Lei An, Qianying Yang, Ruiqi Hai, Guangyin Xi, Yinjuan Wang, Juan Liu, Chao Zhang, Yao Fu, Zhenni Zhang, Xiaodong Wang, Jianhui Tian

{"title":"FGF4 initiates X-chromosome inactivation via activating YY1 and prompting loss of pluripotency factors.","authors":"Lizhu Ma, Wei Fu, Lei An, Qianying Yang, Ruiqi Hai, Guangyin Xi, Yinjuan Wang, Juan Liu, Chao Zhang, Yao Fu, Zhenni Zhang, Xiaodong Wang, Jianhui Tian","doi":"10.1038/s44318-026-00722-2","DOIUrl":"10.1038/s44318-026-00722-2","url":null,"abstract":"X-chromosome inactivation (XCI) balances gene expression between sexes in mammals and is essential to female development. XCI initiation strictly relies on the upregulation of long noncoding RNA Xist upon differentiation. Despite the co-occurrence and tight correlation between XCI and differentiation, master coordinators to synchronize XCI and differentiation remain ill-defined. Here, we report that FGF4, an autocrine differentiation-prompting stimulus, is essential for Xist upregulation and XCI initiation in mouse embryonic stem cells (ESCs). Either Fgf4 deficiency or FGFR blocking results in failure of Xist upregulation and XCI initiation. Mechanistically, FGF4 initiates XCI in a MEK/ERK-dependent manner, via two parallel but opposing pathways: i)FGF4 phosphorylates and activates YY1, a robust transcription activator of Xist, and ii) FGF4 facilitates decline of pluripotency factors Prdm14, Nanog and Rex1, resolving Xist repression. Together, we show how FGF4 comprehensively orchestrates XCI and ESC differentiation, and ensures XCI initiation by coordinating two opposing regulators that directly influence Xist transcription. The FGF-ERK-YY1 axis also constitutes a missing link between ubiquitously expressed Yy1 and its functional activation responsible for Xist upregulation and XCI initiation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3056-3072"},"PeriodicalIF":8.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515885","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

Author Correction: Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses. 作者更正：致瘤性p53突变体的残余凋亡活性改善了癌症治疗反应。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-05-01 Epub Date: 2026-03-24 DOI: 10.1038/s44318-026-00758-4

Oleg Timofeev, Boris Klimovich, Jean Schneikert, Michael Wanzel, Evangelos Pavlakis, Julia Noll, Samet Mutlu, Sabrina Elmshäuser, Andrea Nist, Marco Mernberger, Boris Lamp, Ulrich Wenig, Alexander Brobeil, Stefan Gattenlöhner, Kernt Köhler, Thorsten Stiewe

引用次数: 0

Clean cut to curtail respiration: OMA1 cleaves AIFM1 to tune stress-induced bioenergetics. 清洁切割减少呼吸：OMA1切割AIFM1以调节应激诱导的生物能量。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-30 DOI: 10.1038/s44318-026-00787-z

Muhammad Irfan Afridi, Agnieszka Chacinska

引用次数: 0

Prothrombinase processivity is conferred by substrate allostery. 凝血酶原的加工性是由底物变构引起的。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-22 DOI: 10.1038/s44318-026-00782-4

Fatma Işık Üstok, Alexandre Faille, Alan J Warren, James A Huntington

引用次数: 0

MATCAP1 preferentially binds an expanded tubulin conformation to generate detyrosinated and ΔC2 α-tubulin. MATCAP1优先结合扩展的微管蛋白构象产生去酪氨酸和ΔC2 α-微管蛋白。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-13 DOI: 10.1038/s44318-026-00772-6

Yang Yue, Takashi Hotta, Ryoma Ohi, Kristen J Verhey

{"title":"MATCAP1 preferentially binds an expanded tubulin conformation to generate detyrosinated and ΔC2 α-tubulin.","authors":"Yang Yue, Takashi Hotta, Ryoma Ohi, Kristen J Verhey","doi":"10.1038/s44318-026-00772-6","DOIUrl":"10.1038/s44318-026-00772-6","url":null,"abstract":"Microtubules are cytoskeletal filaments with critical roles in cell division, cell motility, intracellular trafficking, and cilium function. In cells, subsets of microtubules are selectively marked by posttranslational modifications (PTMs) that control the ability of microtubule-associated proteins (MAPs) and molecular motors to engage microtubules. Detyrosination (ΔY) and ΔC2 are PTMs of α-tubulin wherein one or two residues, respectively, are enzymatically removed from the C-terminus of the protein. How specific patterns of PTMs are generated in cells is incompletely understood. Here, we use in vitro reconstitution assays to investigate the microtubule-binding behavior of metallopeptidase MATCAP1 and the mechanism by which it generates ΔY and ΔC2 modifications of α-tubulin. We demonstrate that MATCAP1 preferentially binds to microtubules composed of tubulin subunits in an expanded conformation, which can be induced by preventing β-tubulin GTP hydrolysis, taxol treatment, or kinesin-1 stepping. MATCAP1 exhibits a long dwell-time on microtubules and sequentially removes residues to generate ΔY-microtubules and ΔC2-microtubules. Thus, the lattice conformation of microtubules is a key factor that gates the binding and activity of MATCAP1.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678286","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