Cell reports最新文献_第3页

Structural ubiquitin contributes to K48 linkage specificity of the HECT ligase Tom1. 结构泛素有助于HECT连接酶Tom1的K48连锁特异性。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-12 DOI: 10.1016/j.celrep.2025.115688

Katrina Warner, Moritz Hunkeler, Kheewoong Baek, Anna Schmoker, Shourya S Roy Burman, Daan Overwijn, Cyrus Jin, Katherine A Donovan, Eric S Fischer

{"title":"Structural ubiquitin contributes to K48 linkage specificity of the HECT ligase Tom1.","authors":"Katrina Warner, Moritz Hunkeler, Kheewoong Baek, Anna Schmoker, Shourya S Roy Burman, Daan Overwijn, Cyrus Jin, Katherine A Donovan, Eric S Fischer","doi":"10.1016/j.celrep.2025.115688","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115688","url":null,"abstract":"Homologous to E6AP C terminus (HECT) ubiquitin ligases play key roles in essential pathways such as DNA repair, cell cycle control, or protein quality control. Tom1 is one of five HECT ubiquitin E3 ligases in budding yeast S. cerevisiae and is prototypical for a ligase with pleiotropic functions such as ubiquitin chain amplification, orphan quality control, and DNA damage response. Structures of full-length HECT ligases, including the Tom1 ortholog HUWE1, have been reported, but how domains beyond the conserved catalytic module contribute to catalysis remains largely elusive. Here, through cryoelectron microscopy (cryo-EM) snapshots of Tom1 during an active ubiquitination cycle, we demonstrate that the extended domain architecture directly contributes to activity. We identify a Tom1-ubiquitin architecture during ubiquitination involving a non-canonical ubiquitin-binding site in the solenoid shape of Tom1. We demonstrate that this ubiquitin-binding site coordinates a structural ubiquitin contributing to the fidelity of K48 poly-ubiquitin chain assembly.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115688"},"PeriodicalIF":7.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983096","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

Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia. 癌症诱导的FOXP1破坏和重编程恶病质中骨骼肌昼夜节律转录。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-10 DOI: 10.1016/j.celrep.2025.115689

Jeremy B Ducharme, Daria Neyroud, Martin M Schonk, Miguel A Gutierrez-Monreal, Zhiguang Huo, Haley O Tucker, Karyn A Esser, Sarah M Judge, Andrew R Judge

{"title":"Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia.","authors":"Jeremy B Ducharme, Daria Neyroud, Martin M Schonk, Miguel A Gutierrez-Monreal, Zhiguang Huo, Haley O Tucker, Karyn A Esser, Sarah M Judge, Andrew R Judge","doi":"10.1016/j.celrep.2025.115689","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115689","url":null,"abstract":"Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle wasting in response to cancer. However, transcriptional networks targeted by FoxP1 in skeletal muscles undergoing cancer-induced wasting remain largely unknown. Here, we identify FoxP1 as a key disruptor of the skeletal-muscle clock in response to cancer that reprograms circadian patterns of gene expression at cachexia onset. Specifically, we show that cancer-induced FoxP1 rewires the skeletal-muscle circadian transcriptome toward pathways associated with muscle wasting and disrupts the temporal patterning of pathways governing glucose, lipid, and oxidative metabolism. These findings thus implicate cancer/disease-specific functions of FOXP1 in the disruption and reprograming of the skeletal-muscle circadian transcriptome, which may contribute to muscle wasting and the development of cachexia.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115689"},"PeriodicalIF":7.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981518","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

A multimodal screening platform for endogenous dipeptide repeat proteins in C9orf72 patient iPSC neurons. C9orf72患者iPSC神经元内源性二肽重复蛋白的多模式筛选平台。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-10 DOI: 10.1016/j.celrep.2025.115695

Benedikt V Hölbling, Yashica Gupta, Paolo M Marchi, Magda L Atilano, Michael Flower, Enric Ureña, Rajkumar A Goulden, Hannah K Dobbs, Eszter Katona, Alla Mikheenko, Ashling Giblin, Ali Raza Awan, Chloe L Fisher-Ward, Niamh O'Brien, Deniz Vaizoglu, Liam Kempthorne, Katherine M Wilson, Lauren M Gittings, Mireia Carcolé, Marc-David Ruepp, Sarah Mizielinska, Linda Partridge, Pietro Fratta, Sarah J Tabrizi, Bhuvaneish T Selvaraj, Siddharthan Chandran, Emma Armstrong, Paul Whiting, Adrian M Isaacs

{"title":"A multimodal screening platform for endogenous dipeptide repeat proteins in C9orf72 patient iPSC neurons.","authors":"Benedikt V Hölbling, Yashica Gupta, Paolo M Marchi, Magda L Atilano, Michael Flower, Enric Ureña, Rajkumar A Goulden, Hannah K Dobbs, Eszter Katona, Alla Mikheenko, Ashling Giblin, Ali Raza Awan, Chloe L Fisher-Ward, Niamh O'Brien, Deniz Vaizoglu, Liam Kempthorne, Katherine M Wilson, Lauren M Gittings, Mireia Carcolé, Marc-David Ruepp, Sarah Mizielinska, Linda Partridge, Pietro Fratta, Sarah J Tabrizi, Bhuvaneish T Selvaraj, Siddharthan Chandran, Emma Armstrong, Paul Whiting, Adrian M Isaacs","doi":"10.1016/j.celrep.2025.115695","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115695","url":null,"abstract":"Repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. Repeat-associated non-AUG (RAN) translation generates neurotoxic dipeptide repeat proteins (DPRs). To study endogenous DPRs, we inserted the minimal HiBiT luciferase reporter downstream of sense repeat derived DPRs polyGA or polyGP in C9orf72 patient iPSCs. We show these \"DPReporter\" lines sensitively and rapidly report DPR levels in lysed and live cells and optimize screening in iPSC neurons. Small-molecule screening showed the ERK1/2 activator periplocin dose dependently increases DPR levels. Consistent with this, ERK1/2 inhibition reduced DPR levels and prolonged survival in C9orf72 repeat expansion flies. CRISPR knockout screening of all human helicases revealed telomere-associated helicases modulate DPR expression, suggesting common regulation of telomeric and C9orf72 repeats. These DPReporter lines allow investigation of DPRs in their endogenous context and provide a template for studying endogenous RAN-translated proteins, at scale, in other repeat expansion disorders.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115695"},"PeriodicalIF":7.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968543","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

Haplotype-resolved genomes provide insights into the origins and functional significance of genome diversity in bivalves. 单倍型解析基因组为双壳类动物基因组多样性的起源和功能意义提供了见解。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-10 DOI: 10.1016/j.celrep.2025.115697

Shikai Liu, Chenyu Shi, Chenguang Chen, Ying Tan, Yuan Tian, Daniel J Macqueen, Qi Li

{"title":"Haplotype-resolved genomes provide insights into the origins and functional significance of genome diversity in bivalves.","authors":"Shikai Liu, Chenyu Shi, Chenguang Chen, Ying Tan, Yuan Tian, Daniel J Macqueen, Qi Li","doi":"10.1016/j.celrep.2025.115697","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115697","url":null,"abstract":"Bivalves are famed for exhibiting vast genetic diversity of poorly understood origins and functional significance. Through comparative genomics, we demonstrate that high genetic diversity in these invertebrates is not directly linked to genome size. Using oysters as a representative clade, we show that despite genome size reduction during evolution, these bivalves maintain remarkable genetic variability. By constructing a haplotype-resolved genome for Crassostrea sikamea, we identify widespread haplotype divergent sequences (HDSs), representing genomic regions unique to each haplotype. We show that HDSs are driven by transposable elements, playing a key role in creating and maintaining genetic diversity during oyster evolution. Comparisons of haplotype-resolved genomes across four bivalve orders uncover diverse HDS origins, highlighting a role in genetic innovation and expression regulation across broad timescales. Further analyses show that, in oysters, haplotype polymorphisms drive gene expression variation, which is likely to promote phenotypic plasticity and adaptation. These findings advance our understanding of the relationships among genome structure, diversity, and adaptability in a highly successful invertebrate group.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115697"},"PeriodicalIF":7.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955164","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

Genomic context influences translesion synthesis DNA polymerase-dependent mechanisms of micronuclei induction by G-quadruplexes. 基因组环境影响翻译合成DNA聚合酶依赖机制的微核诱导的g -四联体。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-10 DOI: 10.1016/j.celrep.2025.115706

Simona Pepe, Federico Guerra, Marco Russo, Renée C Duardo, Giovanni Capranico

引用次数: 0

IRE1α promotes phagosomal calcium flux to enhance macrophage fungicidal activity. IRE1α促进吞噬体钙通量，增强巨噬细胞的杀真菌活性。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-09 DOI: 10.1016/j.celrep.2025.115694

Michael J McFadden, Mack B Reynolds, Britton C Michmerhuizen, Einar B Ólafsson, Sofia M Marshall, Faith Anderson Davis, Tracey L Schultz, Takao Iwawaki, Jonathan Z Sexton, Mary X D O'Riordan, Teresa R O'Meara

{"title":"IRE1α promotes phagosomal calcium flux to enhance macrophage fungicidal activity.","authors":"Michael J McFadden, Mack B Reynolds, Britton C Michmerhuizen, Einar B Ólafsson, Sofia M Marshall, Faith Anderson Davis, Tracey L Schultz, Takao Iwawaki, Jonathan Z Sexton, Mary X D O'Riordan, Teresa R O'Meara","doi":"10.1016/j.celrep.2025.115694","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115694","url":null,"abstract":"The mammalian endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) is essential for cellular homeostasis and plays key roles in infection responses, including innate immunity and microbicidal activity. While IRE1α functions through the IRE1α-XBP1S axis are known, its XBP1S-independent roles are less well understood, and its functions during fungal infection are still emerging. We demonstrate that Candida albicans activates macrophage IRE1α via C-type lectin receptor signaling independent of protein misfolding, suggesting non-canonical activation. IRE1α enhances macrophage fungicidal activity by promoting phagosome maturation, which is crucial for containing C. albicans hyphae. IRE1α facilitates early phagosomal calcium flux post-phagocytosis, which is required for phagolysosomal fusion. In macrophages lacking the IRE1α endoribonuclease domain, defective calcium flux correlates with fewer ER-early endosome contact sites, suggesting a homeostatic role for IRE1α-promoting membrane contact sites. Overall, our findings illustrate non-canonical IRE1α activation during infection and a function for IRE1α in supporting organelle contact sites to safeguard against rapidly growing microbes.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115694"},"PeriodicalIF":7.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976251","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

Multitissue single-cell analysis reveals differential cellular and molecular sensitivity between fructose and high-fat high-sucrose diets. 多组织单细胞分析揭示了果糖和高脂肪高蔗糖饮食之间的细胞和分子敏感性差异。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-09 DOI: 10.1016/j.celrep.2025.115690

Yen-Wei Chen, In Sook Ahn, Susanna Sue-Ming Wang, Sana Majid, Graciel Diamante, Ingrid Cely, Guanglin Zhang, Angelus Cabanayan, Sergey Komzyuk, Jack Bonnett, Douglas Arneson, Xia Yang

{"title":"Multitissue single-cell analysis reveals differential cellular and molecular sensitivity between fructose and high-fat high-sucrose diets.","authors":"Yen-Wei Chen, In Sook Ahn, Susanna Sue-Ming Wang, Sana Majid, Graciel Diamante, Ingrid Cely, Guanglin Zhang, Angelus Cabanayan, Sergey Komzyuk, Jack Bonnett, Douglas Arneson, Xia Yang","doi":"10.1016/j.celrep.2025.115690","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115690","url":null,"abstract":"Metabolic syndrome (MetS), a conglomerate of dysregulated metabolic traits that vary between individuals, is partially driven by modern diets high in fat, sucrose, or fructose and their interactions with host genes in metabolic tissues. To elucidate the roles of individual tissues and cell types in diet-induced MetS, we performed single-cell RNA sequencing on the hypothalamus, liver, adipose tissue, and small intestine of mice fed high-fat high-sucrose (HFHS) or fructose diets. We found that hypothalamic neurons were sensitive to fructose, while adipose progenitor cells and macrophages were responsive to HFHS. Ligand-receptor analysis revealed lipid metabolism and inflammation networks among peripheral tissues driven by HFHS, while both diets stimulated synaptic remodeling within the hypothalamus. mt-Rnr2, a top responder to both diets, mitigated diet-induced MetS by stimulating thermogenesis. Our study demonstrates that HFHS and fructose diets have differential cell type and network targets but also share regulators such as mt-Rnr2 to affect MetS risk.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115690"},"PeriodicalIF":7.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978165","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

NANS suppresses NF-κB signaling to promote ferroptosis by perturbing iron homeostasis. NANS通过干扰铁稳态抑制NF-κB信号，促进铁凋亡。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-09 DOI: 10.1016/j.celrep.2025.115701

Ziyang Wang, Yuqin Di, Lvlan Ye, Wenzheng Fang, Xiangqiong Wen, Xiang Zhang, Jiale Qin, Youpeng Wang, Kunhua Hu, Zhenxin Zhu, Weiling He, Ying Chen

{"title":"NANS suppresses NF-κB signaling to promote ferroptosis by perturbing iron homeostasis.","authors":"Ziyang Wang, Yuqin Di, Lvlan Ye, Wenzheng Fang, Xiangqiong Wen, Xiang Zhang, Jiale Qin, Youpeng Wang, Kunhua Hu, Zhenxin Zhu, Weiling He, Ying Chen","doi":"10.1016/j.celrep.2025.115701","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115701","url":null,"abstract":"Metastatic colorectal cancer (CRC) cells endure survival challenges, including treatment-induced ferroptosis. While adaptation to ferroptosis stress facilitates metastasis, reciprocal regulatory mechanisms remain unclear. Here, a CRISPR-Cas9 screen identifies N-acetylneuraminate synthase (NANS) as a ferroptosis promoter in CRC, regardless of its metabolic function. NANS expression is downregulated and correlates with poor prognosis in patients with CRC. Under ferroptotic stress, cyclin-dependent kinase 1 (CDK1) phosphorylates NANS at serine 275 (S275), triggering its dissociation from TAK1. Phosphorylated NANS is ubiquitinated by UBE2N at K246, leading to degradation, which activates TAK1-NF-κB signaling and upregulates the ferroptosis inhibitor FTH1, enabling metastasis via ferroptosis resistance. NANS pS275 levels are associated with tumor aggressiveness and clinical outcomes in patients with CRC. These findings indicate that NANS suppresses CRC metastasis by enhancing ferroptosis susceptibility, while CDK1-mediated phosphorylation at S275 drives adaptive resistance. Targeting this phosphorylation axis may improve ferroptosis-inducing therapies to restrict metastatic progression in CRC.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115701"},"PeriodicalIF":7.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978597","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

Reliable sensory processing of superficial cortical interneurons is modulated by behavioral state. 皮层表层中间神经元的可靠感觉加工受行为状态的调节。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-09 DOI: 10.1016/j.celrep.2025.115678

Carolyn G Sweeney, Maryse E Thomas, Christine Junhui Liu, Lucas G Vattino, Kasey E Smith, Anne E Takesian

{"title":"Reliable sensory processing of superficial cortical interneurons is modulated by behavioral state.","authors":"Carolyn G Sweeney, Maryse E Thomas, Christine Junhui Liu, Lucas G Vattino, Kasey E Smith, Anne E Takesian","doi":"10.1016/j.celrep.2025.115678","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115678","url":null,"abstract":"GABAergic interneurons in cortical layer 1 (L1) integrate sensory and top-down inputs to modulate network activity and support learning-related plasticity. However, little is known about how sensory inputs drive L1 interneuron activity. We used two-photon calcium imaging to measure sound-evoked responses in two L1 interneuron populations expressing vasoactive intestinal peptide (VIP) or neuron-derived neurotrophic factor (NDNF) in mouse auditory cortex. We found that L1 interneurons respond to both simple and complex sounds, but their responses are highly variable across trials. Despite this variability, these interneurons respond reliably to a narrow range of stimuli, reflecting selectivity for specific spectrotemporal sound features. Response reliability was modulated by behavioral state and predicted by the activity of neighboring interneurons. These findings reveal that L1 interneurons exhibit sensory tuning and identify the modulation of response reliability as a potential mechanism by which L1 relays state-dependent cues to shape sensory representations.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115678"},"PeriodicalIF":7.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954128","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

UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation. ufmyation通过调节核糖体解离来保护人肝细胞分化和肝脏稳态。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-05-09 DOI: 10.1016/j.celrep.2025.115686

Shuchun Yang, Li Wang, Ran Gao, Yanchang Li, Duo Zhang, Chenxi Wang, Guang Liu, Jie Na, Ping Xu, Xiaoyue Wang, Yuyan Jia, Yue Huang

{"title":"UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation.","authors":"Shuchun Yang, Li Wang, Ran Gao, Yanchang Li, Duo Zhang, Chenxi Wang, Guang Liu, Jie Na, Ping Xu, Xiaoyue Wang, Yuyan Jia, Yue Huang","doi":"10.1016/j.celrep.2025.115686","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115686","url":null,"abstract":"Ribosomal UFMylation contributes to ribosome heterogeneity and is associated with ribosome-associated quality control at the endoplasmic reticulum. However, the specific pathophysiological functions of ribosomal UFMylation remain unknown. In this study, we systematically demonstrate the significance of UFMylation in the differentiation and maturation of hepatocytes using human embryonic stem cell-derived hepatocyte-like cells and liver bud organoids as experimental platforms. We also develop a strategy to identify UFMylated substrates and confirm that RPL26 is a substrate in the liver. Additionally, we discover that mice with the Rpl26 c.395A>G (p.K132R) mutation are more susceptible to steatosis induced by a high-fat diet. Further investigations reveal a key role of CDK5RAP3 and RPL26 UFMylation in regulating ribosome dissociation. Our findings suggest that ribosome UFMylation serves as an important safeguard for liver development and homeostasis and may represent a potential therapeutic target for nonalcoholic fatty liver disease.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115686"},"PeriodicalIF":7.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960610","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