The EMBO Journal最新文献_第2页

FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5. FUS通过相分离介导的转录因子MEF2和ETV5的募集来控制肌肉分化。

The EMBO Journal Pub Date : 2026-07-22 DOI: 10.1038/s44318-026-00874-1

Gina Picchiarelli,Anne Wienand,Salim Megat,Saskia Hutten,Amr Aly,Marije Been,Isabelle Weber,Angela Bonanno,Nibha Mishra,Erin Sternburg,Pierre Cauchy,Stéphane Dieterle,Marica Catinozzi,Javier Lobo-Mancheno,Hannah Walgrave,Valérie Demais,Pierre Hener,Pascal Kessler,Laura Tzeplaeff,Annemarie Huebers,Dagmar Zeuschner,Angela Rosenbohm,Albert C Ludolph,Anne-Laurence Boutillier,Tobias Boeckers,Dorothee Dormann,Maria Demestre,Chantal Sellier,Clotilde Lagier-Tourenne,Erik Storkebaum,Luc Dupuis

{"title":"FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5.","authors":"Gina Picchiarelli,Anne Wienand,Salim Megat,Saskia Hutten,Amr Aly,Marije Been,Isabelle Weber,Angela Bonanno,Nibha Mishra,Erin Sternburg,Pierre Cauchy,Stéphane Dieterle,Marica Catinozzi,Javier Lobo-Mancheno,Hannah Walgrave,Valérie Demais,Pierre Hener,Pascal Kessler,Laura Tzeplaeff,Annemarie Huebers,Dagmar Zeuschner,Angela Rosenbohm,Albert C Ludolph,Anne-Laurence Boutillier,Tobias Boeckers,Dorothee Dormann,Maria Demestre,Chantal Sellier,Clotilde Lagier-Tourenne,Erik Storkebaum,Luc Dupuis","doi":"10.1038/s44318-026-00874-1","DOIUrl":"https://doi.org/10.1038/s44318-026-00874-1","url":null,"abstract":"FUS is an RNA-binding protein mutated in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive muscle weakness. We show in this work that a heterozygous knock-in mutation in the mouse Fus gene leads to cell-autonomous ultrastructural defects in skeletal muscle, with disruption of sarcomeres and mitochondria. Studies in mouse and Drosophila models demonstrate an evolutionarily conserved cell-autonomous function of FUS in muscle development. Mechanistically, FUS is required for the transcription of MEF2 target genes, binds to the promoter of genes bound by ETS transcription factors, in particular ETV5, and co-activates the transcription of MEF2-dependent genes with ETV5. FUS phase-separates with ETV5 and MEF2A, and stimulation of MEF2-dependent transcription by FUS is dependent upon its phase separation properties. Finally, Etv5 haploinsufficiency exacerbates muscle weakness and atrophy in Fus knock-in mice. Our findings establish a key role for FUS in skeletal muscle differentiation through its phase separation-dependent recruitment of ETV5 and MEF2, defining a novel pathway compromised in FUS-ALS.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atg23 prevents aberrant fusion of Atg9 vesicles during delivery to autophagosome formation sites. Atg23可防止Atg9囊泡在递送至自噬体形成位点时发生异常融合。

The EMBO Journal Pub Date : 2026-07-20 DOI: 10.1038/s44318-026-00867-0

Takumi Kimura,Takayuki Shima,Tetsuya Kotani,Hitoshi Nakatogawa

引用次数: 0

Vps1 drives membrane constriction and fission necessary for endosomal protein sorting. Vps1驱动内体蛋白分选所必需的膜收缩和裂变。

The EMBO Journal Pub Date : 2026-07-20 DOI: 10.1038/s44318-026-00855-4

Shilpa Gopan,Uma Swaminathan,Gurmail Singh,Thomas J Pucadyil

{"title":"Vps1 drives membrane constriction and fission necessary for endosomal protein sorting.","authors":"Shilpa Gopan,Uma Swaminathan,Gurmail Singh,Thomas J Pucadyil","doi":"10.1038/s44318-026-00855-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00855-4","url":null,"abstract":"The trafficking of cargo between endosomes and the Golgi apparatus uses both retromer-dependent and retromer-independent routes. Disruptions to these routes lead to the mis-sorting of lysosomal cargo, and associated metabolic and neurological disorders. The yeast dynamin Vps1 is essential for these trafficking pathways; however, it is not clear whether it directly causes membrane fission. Using cell-free reconstitution and live-cell assays, here we demonstrate that Vps1 assembles into scaffolds on membrane tubules, and uses GTP hydrolysis to force tubule constriction and fission. Vps1 mutants that are unable to assemble or to hydrolyze GTP fail to achieve fission in vitro and cause cargo mis-sorting in vivo. Furthermore, we identify two essential motifs, a lysine-rich phosphoinositide-binding motif and a phenylalanine-rich self-assembly motif, which, when mutated, render Vps1 dysfunctional. Finally, quantitative proteomics revealed a broad range of Golgi and plasma membrane proteins that mis-sort to the vacuole without Vps1. These findings define the Vps1-dependent retrograde pathway's cargo repertoire and confirm Vps1's mechanochemical role in membrane fission.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reactive oxygen species stimulate Paneth cell plasticity and diminish antimicrobial function. 活性氧刺激细胞可塑性，降低抗菌功能。

The EMBO Journal Pub Date : 2026-07-18 DOI: 10.1038/s44318-026-00869-y

Jiaxing Yang,Sheila Bandyopadhyay,Dahui Wang,Edward Gonzalez,Yeqing Chen,Jagannatham Naidu Bhupana,Oscar Pellon-Cardenas,Helen Park,Iyshwarya Balasubramanian,Jared Bianchi-Smak,Xiao Zhang,Zhi Wei,Edward M Bonder,Michael P Verzi,Jean-Pierre Etchegaray,Nan Gao

{"title":"Reactive oxygen species stimulate Paneth cell plasticity and diminish antimicrobial function.","authors":"Jiaxing Yang,Sheila Bandyopadhyay,Dahui Wang,Edward Gonzalez,Yeqing Chen,Jagannatham Naidu Bhupana,Oscar Pellon-Cardenas,Helen Park,Iyshwarya Balasubramanian,Jared Bianchi-Smak,Xiao Zhang,Zhi Wei,Edward M Bonder,Michael P Verzi,Jean-Pierre Etchegaray,Nan Gao","doi":"10.1038/s44318-026-00869-y","DOIUrl":"https://doi.org/10.1038/s44318-026-00869-y","url":null,"abstract":"The gut epithelium faces constant environmental oxidative stresses. How it responds to pathological reactive oxygen species (ROS) is not fully understood. Using Paneth cell (PC) lineage reporters and genetic tracing, we show that as PC progenitors mature, a decline in their oxidative phosphorylation (OXPHOS) activity coincides with an increased capacity to produce antimicrobial peptides (AMPs). Direct stimulation by elevated extracellular ROS, often found during gut infection and inflammation, can drive a subset of PCs into mitotic cell division. Increasing mitochondrial superoxide production via impairment or uncoupling of the respiratory electron transport chain similarly stimulated PC cell-cycle entry and dedifferentiation into various intestinal epithelial cell types. Using gain- and loss-of-function approaches, we found that the Rho-GTPase CDC42 in PCs regulates the balance of ROS and antimicrobial peptide production, influencing the outcome of pathogenic infection. CDC42 deficiency impairs mitochondrial respiration in PCs, elevating cellular ROS, plasticity, and inflammation. Together, ROS directly suppress the mature PC phenotypes, contributing to the widely observed PC pathology in inflammatory diseases. Our findings suggest that molecular defects affecting OXPHOS balance and antimicrobial peptide production in PCs will likely impair innate defense and drive inflammatory progression in the intestine.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148476303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Distinct heterochromatin-like domains promote transcriptional memory and silence parasitic genetic elements in bacteria. 作者更正：不同的异染色质样结构域促进细菌的转录记忆和沉默寄生遗传元件。

The EMBO Journal Pub Date : 2026-07-17 DOI: 10.1038/s44318-026-00860-7

Haley Minami Amemiya,Thomas J Goss,Taylor M Nye,Rebecca Hurto,Lyle A Simmons,Lydia Freddolino

引用次数: 0

Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life. 早期NuA4复合体活性对成人蛋白质停滞和长寿的发育启动作用。

The EMBO Journal Pub Date : 2026-07-16 DOI: 10.1038/s44318-026-00851-8

Yihan Wang,Xiong Xiong,Runshuai Zhang,Long Xiao,Xinyu Ruan,Tianyi Ni,Zicheng Liu,Jie Chen,Shenlu Qin,Zhuo Du,Yanxiao Zhang,Lianfeng Wu

{"title":"Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life.","authors":"Yihan Wang,Xiong Xiong,Runshuai Zhang,Long Xiao,Xinyu Ruan,Tianyi Ni,Zicheng Liu,Jie Chen,Shenlu Qin,Zhuo Du,Yanxiao Zhang,Lianfeng Wu","doi":"10.1038/s44318-026-00851-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00851-8","url":null,"abstract":"Proteostasis collapse, a hallmark of aging and neurodegeneration like Alzheimer's disease (AD), causes irreversible damage in late life. Whether late-life proteostasis capacity is developmentally programmed remains unclear, as mechanistic studies requiring lifelong tracking and molecular manipulation are challenging or impossible in long-lived species. Using C. elegans as a lifelong, genetically tractable AD model, we uncover a critical early-life window during which reducing TIP60/NuA4 acetyltransferase complex activity enduringly enhances proteostasis and extends lifespan. Mechanistically, NuA4 reduction depletes H4K16ac, triggering a compensatory, early-life-biased, XBP-1-mediated unfolded protein response (UPRER). This UPRER activation remodels endoplasmic reticulum (ER) morphology and reprograms lipid metabolism, driving selective oleic acid (OA) accumulation. Crucially, this developmentally-installed OA reservoir confers lasting resilience against proteotoxic stress, an effect mimicked by OA supplementation. Together, these findings establish a chromatin-ER-lipid axis that developmentally primes adult proteostasis and suggest early-life interventions as a strategy to promote healthy aging and resilience to proteotoxic stress.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic buffering restricts phenotype switching in melanoma. 代谢缓冲限制了黑色素瘤的表型转换。

The EMBO Journal Pub Date : 2026-07-15 DOI: 10.1038/s44318-026-00857-2

Ana Ramírez-Sánchez,Miguel Jociles-Ortega,José Manuel García-Martínez,Irene Torrens-Martínez,Javier Martínez-Useros,Pakavarin Louphrasitthiphol,Mollie I Sweeney,Ana Morente-Carrasco,Sergio Ruiz-Reyes,Nerea Redondo-Díaz,Teresa Olmos-De Blas,María Jesús Fernández-Aceñero,José N Rodriguez-López,Tomoyoshi Soga,Richard M White,Colin R Goding,Luis Sanchez-Del-Campo,Custodia García-Jiménez,Ana Chocarro-Calvo

{"title":"Metabolic buffering restricts phenotype switching in melanoma.","authors":"Ana Ramírez-Sánchez,Miguel Jociles-Ortega,José Manuel García-Martínez,Irene Torrens-Martínez,Javier Martínez-Useros,Pakavarin Louphrasitthiphol,Mollie I Sweeney,Ana Morente-Carrasco,Sergio Ruiz-Reyes,Nerea Redondo-Díaz,Teresa Olmos-De Blas,María Jesús Fernández-Aceñero,José N Rodriguez-López,Tomoyoshi Soga,Richard M White,Colin R Goding,Luis Sanchez-Del-Campo,Custodia García-Jiménez,Ana Chocarro-Calvo","doi":"10.1038/s44318-026-00857-2","DOIUrl":"https://doi.org/10.1038/s44318-026-00857-2","url":null,"abstract":"The impact of the metabolic microenvironment on epigenetically plastic cancer cells underpins phenotypic heterogeneity, a major cause of metastasis and therapy resistance. Nutrient limitation is a key microenvironmental stress, and can cause cells to transition from proliferative to invasive phenotypes, however, whether cancer cells have the capacity to delay phenotype switching remains unknown. Here, using melanoma as a model, we reveal that the ability to buffer glucose availability by accumulating and mobilizing glycogen can determine cancer cell phenotypic transitions. While proliferating cells contain high levels of glycogen, invasive cells are marked by depleted glycogen stores. Accordingly, the inability to store and metabolize glycogen leads to phenotype instability and a switch from proliferation to invasion. The amount of stored glycogen inversely correlates with tissue invasion depth in primary melanomas, and reduced expression of the glycogen phosphorylases PYGB/L and phosphoglucomutase 1 (PGM1) is associated with worse patient survival. Together, we identify metabolic glucose buffering as a determinant of invasive phenotype transitions in skin cancer, suggesting similar paradigms in other cancer types.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A conserved basic motif mediates membrane anchoring and TRAF2 recruitment across costimulatory TNFRs. 一个保守的基本基序介导共刺激tnfr的膜锚定和TRAF2募集。

The EMBO Journal Pub Date : 2026-07-15 DOI: 10.1038/s44318-026-00868-z

Jiali Zhu,Xi Xu,Pei Liu,Hui Wu,Yuxuan Wang,Boying Xu,Maorong Wen,Min Chen,Zhifeng Chen,James J Chou,Linlin Zhao

{"title":"A conserved basic motif mediates membrane anchoring and TRAF2 recruitment across costimulatory TNFRs.","authors":"Jiali Zhu,Xi Xu,Pei Liu,Hui Wu,Yuxuan Wang,Boying Xu,Maorong Wen,Min Chen,Zhifeng Chen,James J Chou,Linlin Zhao","doi":"10.1038/s44318-026-00868-z","DOIUrl":"https://doi.org/10.1038/s44318-026-00868-z","url":null,"abstract":"Costimulatory receptors of the TNFR superfamily are key components in synthetic immunoreceptors, yet how their intracellular domains coordinate membrane anchoring with adaptor recruitment remains unresolved. Here, using solution-state NMR and membrane-reconstituted FRET assays, we identify a conserved basic-residue-rich sequence (BRS) in the juxtamembrane region of OX40 that binds anionic phospholipids and adopts a membrane-inserted conformation. This membrane engagement enables a dual-site interaction with TRAF2, combining canonical PxQxx binding with a secondary membrane-proximal interface, to promote robust NF-κB activation. Disruption of the BRS impairs adaptor docking without reducing receptor surface expression or ligand-induced clustering. This regulatory architecture is further supported in 4-1BB and CD40, indicating broader relevance across TNFR costimulatory receptors. Our findings refine current models of TNFR signaling and offer a generalizable framework for receptor design. Incorporating membrane-anchoring motifs into synthetic constructs may enhance spatial control of adaptor recruitment, thereby improving signal fidelity, sensitivity, and performance in CAR-T applications.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"362 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CDK8 remodels the tumor microenvironment and promotes resistance to KRASG12D inhibitors and daraxonrasib in PDAC. CDK8重塑肿瘤微环境，促进PDAC对KRASG12D抑制剂和daraxonrasib的耐药性。

The EMBO Journal Pub Date : 2026-07-11 DOI: 10.1038/s44318-026-00854-5

Kathleen M McAndrews,Krishnan K Mahadevan,Bingrui Li,Anaïs M Comptdaer,Amari M Sockwell,Sami J Morse,Patience J Kelly,Sarah I Patel,Michelle L Kirtley,Barbara A Moreno Diaz,Hengyu Lyu,David H Peng,Sima Khazaei,Aislyn Schalck,Xunian Zhou,Hikaru Sugimoto,Aaron A Bickert,Lakshmi Kavitha Sthanam,Meagan R Taylor,Shreyasee V Kumbhar,Kent A Arian,Yasaman Barekatain,Francesca Paradiso,Paola A Guerrero,Vincent Bernard,Navid Sobhani,Alondra N Camacho-Acevedo,Kiara E Bornes,Phuong Thao Tran,Anirban Maitra,Timothy P Heffernan,Raghu Kalluri

{"title":"CDK8 remodels the tumor microenvironment and promotes resistance to KRASG12D inhibitors and daraxonrasib in PDAC.","authors":"Kathleen M McAndrews,Krishnan K Mahadevan,Bingrui Li,Anaïs M Comptdaer,Amari M Sockwell,Sami J Morse,Patience J Kelly,Sarah I Patel,Michelle L Kirtley,Barbara A Moreno Diaz,Hengyu Lyu,David H Peng,Sima Khazaei,Aislyn Schalck,Xunian Zhou,Hikaru Sugimoto,Aaron A Bickert,Lakshmi Kavitha Sthanam,Meagan R Taylor,Shreyasee V Kumbhar,Kent A Arian,Yasaman Barekatain,Francesca Paradiso,Paola A Guerrero,Vincent Bernard,Navid Sobhani,Alondra N Camacho-Acevedo,Kiara E Bornes,Phuong Thao Tran,Anirban Maitra,Timothy P Heffernan,Raghu Kalluri","doi":"10.1038/s44318-026-00854-5","DOIUrl":"https://doi.org/10.1038/s44318-026-00854-5","url":null,"abstract":"Mutations in KRAS are a dominant driver of pancreatic ductal adenocarcinoma (PDAC), with about 50% of patients presenting with KRASG12D mutations. Small molecule inhibitors targeting KRASG12D suppress PDAC; however, the contribution of the tumor microenvironment (TME) to the sustained efficacy of KRASG12D inhibition and mechanisms of resistance to KRASG12D suppression remain to be elucidated. Here, integrated spatial transcriptomics, single-cell RNA sequencing, and CODEX-based spatial proteomics analyses of PDAC mouse models uncover that while KRASG12D inhibition by MRTX1133 initially increases CD11c+ cells and T cell infiltration proximal to cancer cells, long-term treatment results in reversal of the immune responses leading to resistance promoted by multiprotein mediator complex associated kinase CDK8. CDK8 imparts this resistance via induction of CXCL2 chemokine secretion, inhibition of FAS expression, and remodeling of the TME to promote immune evasion. Targeting CDK8 by itself or in combination with αCTLA-4 immunotherapy overcomes resistance to KRASG12D inhibition. We also provide evidence of CDK8 upregulation in PDX tumors resistant to inhibitors selective for RAS(ON) and RASG12D(ON): daraxonrasib and zoldonrasib, respectively, highlighting a common KRAS vulnerability node for TME resistance.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The EMBO Journal Pub Date : 2026-07-11 DOI: 10.1038/s44318-026-00858-1

Onur Deniz,Ying Liu,Tuuli Kirkinen,Krista Kokki,Kateryna Gaertner,Pau Clavell-Revelles,Jaakko Mattila,Ville Hietakangas

{"title":"Spalt-related is an inhibitor of mTORC1-mediated growth activated by the integrated stress response.","authors":"Onur Deniz,Ying Liu,Tuuli Kirkinen,Krista Kokki,Kateryna Gaertner,Pau Clavell-Revelles,Jaakko Mattila,Ville Hietakangas","doi":"10.1038/s44318-026-00858-1","DOIUrl":"https://doi.org/10.1038/s44318-026-00858-1","url":null,"abstract":"Anabolic and catabolic processes are coordinated by a conserved regulatory network, which includes the nutrient-sensing protein kinase mTOR complex 1 (mTORC1) and the insulin- and stress-responsive transcription factor FoxO. In a physiological setting, these regulators align growth, storage, reproduction, and aging with nutrient availability. Here, we identify transcription factor Spalt-related (Salr), previously implicated in organogenesis, as a negative regulator of growth and lipid storage in Drosophila melanogaster. Salr activates catabolic gene expression and restricts mTORC1-mediated cell growth in the Drosophila fat body. The genomic binding of Salr overlaps extensively with that of FoxO, and a similar convergence is observed for their mammalian homologs, SALL1 and FOXO1. Both Salr and FoxO are activated upon fasting, but respond to distinct cues: while FoxO displays transient activation and is responsive to AKT inhibition, Salr is activated in a slow and sustained manner through the integrated stress response. Once activated, Salr counters nuclear localization of FoxO. Taken together, we show that Salr and FoxO are growth-inhibitory transcription factors that act in a convergent manner to respond to nutrient stress through distinct cues.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0