Cell reports最新文献_第9页

The CUP pilus SMF-1 utilizes a specific antiparallel bundling mechanism to initiate biofilm formation. CUP菌毛SMF-1利用一种特殊的反平行捆绑机制来启动生物膜的形成。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-01 DOI: 10.1016/j.celrep.2026.118075

Jessie Lynda Fields, Caitlyn C Sebastian, Hua Zhang, Radhika Bhaumik, Ayisha Zia, Abigail N Robertson, Gregory G Anderson, Seema Mattoo, Hui Wu, Megan R Kiedrowski, Fengbin Wang

{"title":"The CUP pilus SMF-1 utilizes a specific antiparallel bundling mechanism to initiate biofilm formation.","authors":"Jessie Lynda Fields, Caitlyn C Sebastian, Hua Zhang, Radhika Bhaumik, Ayisha Zia, Abigail N Robertson, Gregory G Anderson, Seema Mattoo, Hui Wu, Megan R Kiedrowski, Fengbin Wang","doi":"10.1016/j.celrep.2026.118075","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118075","url":null,"abstract":"Bacterial biofilms enable microbial communities to withstand environmental stress and antibiotic challenge. Stenotrophomonas maltophilia is an opportunistic pathogen that frequently colonizes cystic fibrosis airways. Its chaperone-usher pathway (CUP) pilus, SMF-1, is essential for biofilm development, but its molecular architecture has remained unknown. Here, we present a 4.0 Å cryogenic electron microscopy (cryo-EM) structure demonstrating that the classic γ4 CUP pilus SMF-1 assembles into zigzag filaments that pair into antiparallel \"pili couples\" and higher order bundles. These bundles serve as intercellular tethers that drive rapid cell aggregation during biofilm initiation. Despite belonging to the classic CUP family, SMF-1 lacks the subunit interfaces required for canonical rod-like architectures, providing structural evidence of convergent evolution toward archaic-like biofilm bundling mechanisms. Furthermore, appendage-driven motility acts synergistically with SMF-1 pili to accelerate intercellular encounters and aggregate assembly. Together, these findings reveal a structural mechanism of pilus-mediated crosslinking promoting bacterial colonization.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118075"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103540","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

Progressive remodeling of global protein interaction networks in a mouse model of tauopathy. 牛头病小鼠模型中整体蛋白相互作用网络的进行性重塑。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-01 DOI: 10.1016/j.celrep.2026.118084

Weiwei Lin, Sadhna Phanse, Sophie J F van der Spek, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

{"title":"Progressive remodeling of global protein interaction networks in a mouse model of tauopathy.","authors":"Weiwei Lin, Sadhna Phanse, Sophie J F van der Spek, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin","doi":"10.1016/j.celrep.2026.118084","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118084","url":null,"abstract":"Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes at scale. By revealing how phosphorylation tunes macromolecular complex architecture and function, this work highlights dynamic network instability that develops over the course of tauopathy, and establishes a generalizable framework for mechanistic dissection of functional complexes in neurodegeneration.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118084"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104787","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 non-canonical redox family protein regulates bacterial interaction machineries. 非规范氧化还原家族蛋白调节细菌相互作用机制。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-01 DOI: 10.1016/j.celrep.2026.118071

Rishav Barman, Amit K Baidya

{"title":"A non-canonical redox family protein regulates bacterial interaction machineries.","authors":"Rishav Barman, Amit K Baidya","doi":"10.1016/j.celrep.2026.118071","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118071","url":null,"abstract":"Flagella and nanotubes are two major bacterial apparatuses involved in driving bacterial interactions. Flagella enable cells to perform exploratory roles, whereas nanotubes physically connect nearby cells, facilitating direct transfer of cytoplasmic materials. The only known regulatory protein in Bacillus subtilis that modulates nanotube biogenesis is metallophosphodiesterase YmdB, a global effector, through a route largely elusive. We report that YmdB recruits YdzF for nanotube production. YdzF is a MarR/DUF24 family transcriptional regulator belonging to MarR superfamily required for oxidative stress adaptation, a phenomenon executed by redox-sensing cysteine switches. However, YdzF behaves non-canonically due to proximally positioned intermolecular cysteine residues, hindering its conformational rearrangement. Independent of redox sensing, YdzF recognizes an unrelated flagellar Pfla/che promoter to modulate fla/che operon expression required for nanotube and flagella biogenesis. This promoter recognition by YdzF is entirely governed by YmdB. Furthermore, YdzF-mediated nanotube formation is widespread in Gram-positive bacteria.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118071"},"PeriodicalIF":7.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104693","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

Lysophospholipase PNPLA7 is a critical checkpoint of phosphatidylcholine catabolism and turnover for skeletal muscle homeostasis. 溶血磷脂酶PNPLA7是骨骼肌内稳态中磷脂酰胆碱分解代谢和转换的关键检查点。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-30 DOI: 10.1016/j.celrep.2026.118003

Shoya Matsumoto, Heeyoon Seo, Yoshitaka Taketomi, Takayoshi Higashi, Yuki Nagasaki, Hiroyasu Sato, Mai Kawaguchi, Yasumasa Nishito, Jonguk Park, Kenji Mizuguchi, Koji Hosomi, Jun Kunisawa, Kaori Saito, Keiko Kato, Tomoyoshi Soga, Tetsuya Hirabayashi, Sumito Ogawa, Makoto Murakami

{"title":"Lysophospholipase PNPLA7 is a critical checkpoint of phosphatidylcholine catabolism and turnover for skeletal muscle homeostasis.","authors":"Shoya Matsumoto, Heeyoon Seo, Yoshitaka Taketomi, Takayoshi Higashi, Yuki Nagasaki, Hiroyasu Sato, Mai Kawaguchi, Yasumasa Nishito, Jonguk Park, Kenji Mizuguchi, Koji Hosomi, Jun Kunisawa, Kaori Saito, Keiko Kato, Tomoyoshi Soga, Tetsuya Hirabayashi, Sumito Ogawa, Makoto Murakami","doi":"10.1016/j.celrep.2026.118003","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118003","url":null,"abstract":"Current evidence suggests that disturbed phosphatidylcholine (PC) turnover causes skeletal muscle dysfunction. However, the enzyme that converts lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC), an irreversible checkpoint in PC catabolism, in skeletal muscle has remained unidentified. Here we show that PNPLA7, a patatin-like phospholipase isoform, is responsible for this process. Pnpla7 deletion in myoblasts impedes the conversion of LPC to GPC and then to choline. Quadriceps muscles in global Pnpla7-deficient mice display thinner muscle fibers with aberrant mitochondrial morphology, reduced endurance capacity, and decreased expression of genes related to fatty acid β-oxidation, mitochondrial functions, and slow-twitch fibers with age. These abnormalities are preceded by alterations in phospholipid composition, with decreases in docosahexaenoic acid-containing PC and mitochondrial cardiolipin. Moreover, skeletal muscle-specific Pnpla7 deficiency results in muscle phenotypes similar to its global deficiency. Identification of the lysophospholipase PNPLA7 aids further understanding of the role of PC turnover in skeletal muscle homeostasis.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"118003"},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104713","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

USP-48 enables insulin-mediated longevity and modulates the mitochondrial stress response. USP-48使胰岛素介导的长寿和调节线粒体应激反应。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-30 DOI: 10.1016/j.celrep.2026.118067

Sergio Gordillo-García, Jesus Fernandez-Abascal, Blanca Hernando-Rodríguez, María Jesús Rodríguez-Palero, Laura Cantalejo-Carrasco, Aitor Jarit-Cabanillas, Manuel D Martínez-Bueno, Mercedes M Pérez-Jiménez, Enrique J Clavijo-Bernal, Aitana Cambón, Ildefonso Cases, Matthias Eder, Marta Artal-Sanz

{"title":"USP-48 enables insulin-mediated longevity and modulates the mitochondrial stress response.","authors":"Sergio Gordillo-García, Jesus Fernandez-Abascal, Blanca Hernando-Rodríguez, María Jesús Rodríguez-Palero, Laura Cantalejo-Carrasco, Aitor Jarit-Cabanillas, Manuel D Martínez-Bueno, Mercedes M Pérez-Jiménez, Enrique J Clavijo-Bernal, Aitana Cambón, Ildefonso Cases, Matthias Eder, Marta Artal-Sanz","doi":"10.1016/j.celrep.2026.118067","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118067","url":null,"abstract":"The mitochondrial prohibitin (PHB) complex is essential for mitochondrial homeostasis, yet its depletion produces opposite effects on lifespan: shortening it in wild-type C. elegans but extending it in insulin/IGF-1 receptor daf-2 mutants, which show an attenuated mitochondrial unfolded protein response (UPRmt). To identify regulators of this differential stress response and its role in aging, we conducted the first genome-wide double-RNAi screen in C. elegans. We identify the ubiquitin-specific peptidase USP-48 as a modulator of the UPRmt, specially required for lifespan extension under reduced insulin signaling. USP-48 influences mitochondrial structure and function and cooperates with the transcription factor DVE-1 to regulate the UPRmt largely independent of activating transcription factor associated with stress-1 (ATFS-1). Tissue-specific analysis shows that USP-48 is required for lifespan primarily in the hypodermis, with a smaller germline contribution, but is dispensable in muscle and intestine. Mechanistically, USP-48 promotes histone H2B deubiquitination to shape stress-responsive transcription, revealing ubiquitination as a key determinant of metabolism-dependent longevity.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118067"},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104589","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

Distinct phases of immune system programming during ART-suppressed immunodeficiency virus infection. 抗逆转录病毒抑制免疫缺陷病毒感染期间免疫系统编程的不同阶段。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-30 DOI: 10.1016/j.celrep.2026.118035

Maanasa Kaza, Benjamin Varco-Merth, G W McElfresh, Sebastian Benjamin, Gregory J Boggy, Morgan Chaunzwa, Shana Feltham, Sohita Ojha, Karina Belica, Andrea N Selseth, Michael Nekorchuk, Kathleen Busman-Sahay, Brandon F Keele, Dan H Barouch, Jeffrey D Lifson, Jacob D Estes, Scott G Hansen, Afam A Okoye, Louis J Picker, Benjamin N Bimber

{"title":"Distinct phases of immune system programming during ART-suppressed immunodeficiency virus infection.","authors":"Maanasa Kaza, Benjamin Varco-Merth, G W McElfresh, Sebastian Benjamin, Gregory J Boggy, Morgan Chaunzwa, Shana Feltham, Sohita Ojha, Karina Belica, Andrea N Selseth, Michael Nekorchuk, Kathleen Busman-Sahay, Brandon F Keele, Dan H Barouch, Jeffrey D Lifson, Jacob D Estes, Scott G Hansen, Afam A Okoye, Louis J Picker, Benjamin N Bimber","doi":"10.1016/j.celrep.2026.118035","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118035","url":null,"abstract":"People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can face non-AIDS complications, partially driven by chronic immune activation. To define immune perturbations during ART-suppressed viral infection, we performed longitudinal single-cell transcriptomic and plasma proteomic analyses of rhesus macaques infected with SIVmac239M and treated with ART for 70 weeks. We identified broad, bi-phasic immune changes. Acute infection involves an interferon-driven signature, correlated with viral replication, which largely resolves with viral control. Cell-associated virus correlated with interferon-stimulated genes in most tissues; however, this was blunted in gut-associated lymph nodes, a feature that may contribute to reservoir persistence. Separate alterations manifest 54-66 weeks post-infection, after 40 weeks of viral suppression, including broad TGF-β and NF-κB signaling and discrete bursts of inflammatory monocytes, largely restricted to bone marrow. These data highlight the bi-phasic remodeling of long-term ART-suppressed HIV, identifying specific tissues and cell populations with dysregulation, with implications for the treatment of PLWH.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118035"},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104734","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

Vpu protects HIV-infected cells from antibody-dependent cellular phagocytosis by counteracting tetherin. Vpu通过对抗tetherin保护hiv感染细胞免受抗体依赖性细胞吞噬。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-30 DOI: 10.1016/j.celrep.2026.118080

Brian J Snow, Nida K Keles, Ahmed Ali, Ryan T Behrens, Sanath Kumar Janaka, David T Evans

{"title":"Vpu protects HIV-infected cells from antibody-dependent cellular phagocytosis by counteracting tetherin.","authors":"Brian J Snow, Nida K Keles, Ahmed Ali, Ryan T Behrens, Sanath Kumar Janaka, David T Evans","doi":"10.1016/j.celrep.2026.118080","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118080","url":null,"abstract":"Tetherin is an interferon-inducible transmembrane protein that inhibits the detachment of enveloped viruses from infected cells. HIV-1 Vpu counteracts this restriction by removing tetherin from sites of virus release. Accordingly, Vpu mutations that disrupt tetherin antagonism increase Env accumulation on the surface of HIV-infected cells. We found that Vpu mutations that impair tetherin antagonism also increase the susceptibility of HIV-infected cells to antibody-dependent cellular phagocytosis (ADCP). Increased sensitivity to ADCP was lost in tetherin-knockout cells and conditionally restored by doxycycline-inducible tetherin. Thus, Vpu protects HIV-infected cells from ADCP by preventing virion accumulation on the cell surface, similar to its protection against antibody-dependent cellular cytotoxicity (ADCC). By serving as a link between innate and adaptive immunity, the antiviral activity of tetherin may be amplified in vivo by Fc-mediated antibody effector functions and therefore much greater than initially appreciated based solely on its ability to inhibit virus release in cell culture assays.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118080"},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104581","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

Collapse of embryonic identities and emergence of functional diversity during motor neuron maturation. 运动神经元成熟过程中胚胎身份的瓦解和功能多样性的出现。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-30 DOI: 10.1016/j.celrep.2026.118062

Yijia Chen, Hsuan-Ming Chi, Aileen Tian, Courtney Stains, Alison Miller, Tulsi Patel

{"title":"Collapse of embryonic identities and emergence of functional diversity during motor neuron maturation.","authors":"Yijia Chen, Hsuan-Ming Chi, Aileen Tian, Courtney Stains, Alison Miller, Tulsi Patel","doi":"10.1016/j.celrep.2026.118062","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118062","url":null,"abstract":"Post-mitotic neurons undergo a protracted maturation period as they extend axons to their targets, form synapses, and refine electrophysiological properties. We use temporal single-nucleus multiome sequencing to map molecular underpinnings of maturation in mouse skeletal motor neurons (SMNs). Our data show that SMNs undergo transcriptional changes as they mature, but more strikingly, we find that diversity within SMNs changes dramatically as they transition from axon targeting to forming functional circuits. Embryonic SMNs comprise dozens of transcriptional subclusters representing known motor columns and pools, which utilize specific transcriptional programs to innervate unique muscle targets. However, this transcriptional diversity is largely lost by early postnatal life, and SMNs re-diversify into adult alpha, gamma, and type3 identities, which innervate different fibers within each muscle to regulate movement. This work shows that transcriptional subtype diversity within a neuron type, and the underlying regulatory programs, can transform completely during maturation to accommodate changing functional needs.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118062"},"PeriodicalIF":7.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104677","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 head-mounted open-source light field microscope for large volumetric Ca²⁺ imaging during exploratory and social behavior in mice. 一种头戴式开源光场显微镜，用于小鼠探索和社会行为期间的大体积Ca2+成像。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-29 DOI: 10.1016/j.celrep.2026.118066

Hao Li, Tobias Nöbauer, Hossein Sarafraz, Alipasha Vaziri

{"title":"A head-mounted open-source light field microscope for large volumetric Ca2+ imaging during exploratory and social behavior in mice.","authors":"Hao Li, Tobias Nöbauer, Hossein Sarafraz, Alipasha Vaziri","doi":"10.1016/j.celrep.2026.118066","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118066","url":null,"abstract":"Capturing neuronal activity during natural behaviors in unrestrained animals is critical for understanding brain function, yet existing imaging systems struggle to combine volumetric field-of-view (v-FOV), high resolution, depth, and usability. We present MiniLFMv2, a lightweight, next-generation miniaturized light field microscope enabling volumetric imaging with a v-FOV of ⌀1 × 0.2 mm3, volume rates of up to 30 Hz and depth to ∼350-400 μm. MiniLFMv2 achieves near-diffraction-limited performance, with a working distance of 1 mm. Its custom aspheric lenses and electrically tunable lens eliminate the need for GRIN optics, improving compatibility with cranial window imaging. Applying MiniLFMv2 in freely moving mice, we captured activity from hundreds of parietal cortex neurons at depths up to ∼400 μm with minimal impact on mobility. During exploratory and social behaviors, we identified subpopulations selectively tuned to locomotion, rearing, and social investigation. MiniLFMv2 offers a powerful tool for investigating neural dynamics during naturalistic and social behaviors.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118066"},"PeriodicalIF":7.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079861","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

MTAP loss upregulates BCAT1 in pancreatic cancer and drives branched-chain amino acid dependency. MTAP缺失在胰腺癌中上调BCAT1并驱动支链氨基酸依赖。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-09-29 DOI: 10.1016/j.celrep.2026.118046

Yuling Sheng, Lianhui Duan, Qi Liu, Yihuizhi Zhang, Yanyun Chang, Jingyu Yan, Haoyuan Tan, Zexuan Wang, Yanlin Xiao, Yiping He, Kaisheng Liu, Xin Hong, Siyuan Xia, Wenyong Zhang, Changzheng Du

{"title":"MTAP loss upregulates BCAT1 in pancreatic cancer and drives branched-chain amino acid dependency.","authors":"Yuling Sheng, Lianhui Duan, Qi Liu, Yihuizhi Zhang, Yanyun Chang, Jingyu Yan, Haoyuan Tan, Zexuan Wang, Yanlin Xiao, Yiping He, Kaisheng Liu, Xin Hong, Siyuan Xia, Wenyong Zhang, Changzheng Du","doi":"10.1016/j.celrep.2026.118046","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118046","url":null,"abstract":"Methylthioadenosine phosphorylase (MTAP) deficiency is prevalent in pancreatic ductal adenocarcinoma (PDAC). Herein, we reveal that MTAP loss in PDAC induces a branched-chain amino acid (BCAA) dependency by upregulating the expression of BCAA transaminase 1 (BCAT1) through DNA demethylation. We establish that BCAT1 upregulation promotes cell proliferation and migration in PDAC by fueling the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) via BCAA consumption. Moreover, the BCAA dependency contributes to a more aggressive phenotype via activation of cancer-associated pathways. In addition, the BCAT1 inhibitor BAY-069 demonstrates remarkable therapeutic efficacy in MTAP-deficient PDAC by diminishing the BCAA-facilitated OXPHOS. Finally, clinical analysis reveals an inverse correlation between MTAP and BCAT1 expression in PDAC, and high BCAT1 expression is associated with poor prognosis in patients with PDAC. Collectively, these findings identify the role of BCAT1 as a key regulator mediating metabolic reprogramming in MTAP-deficient PDAC and support BCAT1 as a potential therapeutic target.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118046"},"PeriodicalIF":7.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104773","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