Nature Cell Biology最新文献_第3页

GPX4 methylation puts a brake on ferroptosis

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-21 DOI: 10.1038/s41556-025-01640-x

Graeme I. Lancaster, Andrew J. Murphy

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Breaking up translation condensates in cancer

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-20 DOI: 10.1038/s41556-025-01636-7

Joanna R. Kovalski, Davide Ruggero

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Selective translational control by PABPC1 phase separation regulates blast crisis and therapy resistance in chronic myeloid leukaemia

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-18 DOI: 10.1038/s41556-024-01607-4

Chenguang Sun, Xi Xu, Zhongyang Chen, Fanqi Zhou, Wen Wang, Junzhu Chen, Mengyao Sun, Fang Wang, Linjia Jiang, Ming Ji, Siqi Liu, Jiayue Xu, Manman He, Bowei Su, Xiaoling Liu, Yingdai Gao, Hui Wei, Jian Li, Xiaoshuang Wang, Meng Zhao, Jia Yu, Yanni Ma

{"title":"Selective translational control by PABPC1 phase separation regulates blast crisis and therapy resistance in chronic myeloid leukaemia","authors":"Chenguang Sun, Xi Xu, Zhongyang Chen, Fanqi Zhou, Wen Wang, Junzhu Chen, Mengyao Sun, Fang Wang, Linjia Jiang, Ming Ji, Siqi Liu, Jiayue Xu, Manman He, Bowei Su, Xiaoling Liu, Yingdai Gao, Hui Wei, Jian Li, Xiaoshuang Wang, Meng Zhao, Jia Yu, Yanni Ma","doi":"10.1038/s41556-024-01607-4","DOIUrl":"https://doi.org/10.1038/s41556-024-01607-4","url":null,"abstract":"<p>Tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 fusion tyrosine kinase have revolutionized the treatment of chronic myeloid leukaemia (CML). However, the development of TKI resistance and the subsequent transition from the chronic phase (CP) to blast crisis (BC) threaten patients with CML. Accumulating evidence suggests that translational control is crucial for cancer progression. Our high-throughput CRISPR–Cas9 screening identified poly(A) binding protein cytoplasmic 1 (PABPC1) as a driver for CML progression in the BC stage. PABPC1 preferentially improved the translation efficiency of multiple leukaemogenic mRNAs with long and highly structured 5′ untranslated regions by forming biomolecular condensates. Inhibiting PABPC1 significantly suppressed CML cell proliferation and attenuated disease progression, with minimal effects on normal haematopoiesis. Moreover, we identified two PABPC1 inhibitors that inhibited BC progression and overcame TKI resistance in murine and human CML. Overall, our work identifies PABPC1 as a selective translation enhancing factor in CML-BC, with its genetic or pharmacological inhibition overcoming TKI resistance and suppressed BC progression.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"69 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640507","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

Taking on Parkinson’s

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-14 DOI: 10.1038/s41556-025-01645-6

Stylianos Lefkopoulos

引用次数: 0

Nutrients shape T cell exhaustion

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-14 DOI: 10.1038/s41556-025-01644-7

George Andrew S. Inglis

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Mitochondrial genetics, signalling and stress responses

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-10 DOI: 10.1038/s41556-025-01625-w

Yasmine J. Liu, Jonathan Sulc, Johan Auwerx

{"title":"Mitochondrial genetics, signalling and stress responses","authors":"Yasmine J. Liu, Jonathan Sulc, Johan Auwerx","doi":"10.1038/s41556-025-01625-w","DOIUrl":"10.1038/s41556-025-01625-w","url":null,"abstract":"Mitochondria are multifaceted organelles with crucial roles in energy generation, cellular signalling and a range of synthesis pathways. The study of mitochondrial biology is complicated by its own small genome, which is matrilineally inherited and not subject to recombination, and present in multiple, possibly different, copies. Recent methodological developments have enabled the analysis of mitochondrial DNA (mtDNA) in large-scale cohorts and highlight the far-reaching impact of mitochondrial genetic variation. Genome-editing techniques have been adapted to target mtDNA, further propelling the functional analysis of mitochondrial genes. Mitochondria are finely tuned signalling hubs, a concept that has been expanded by advances in methodologies for studying the function of mitochondrial proteins and protein complexes. Mitochondrial respiratory complexes are of dual genetic origin, requiring close coordination between mitochondrial and nuclear gene-expression systems (transcription and translation) for proper assembly and function, and recent findings highlight the importance of the mitochondria in this bidirectional signalling. Auwerx and colleagues review recent advances in mitochondrial genetics, proteomics and biochemistry that emphasize the far-reaching impact of mitochondrial genetic variation and the role of mitochondria as finely tuned signalling hubs.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 3","pages":"393-407"},"PeriodicalIF":17.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582975","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

Measuring and manipulating mechanical forces during development

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-10 DOI: 10.1038/s41556-025-01632-x

Clémentine Villeneuve, Kaitlin P. McCreery, Sara A. Wickström

引用次数: 0

Unravelling the endoplasmic reticulum–Golgi intermediate compartment in plant cells

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-05 DOI: 10.1038/s41556-025-01629-6

引用次数: 0

Sugar unmasking for trafficking

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-04 DOI: 10.1038/s41556-025-01615-y

David A. Calderwood, Derek Toomre

引用次数: 0

ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-03-03 DOI: 10.1038/s41556-025-01627-8

Yuran Duan, Zhiqiang Hu, Peng Han, Bo Lei, Shuo Wang, Zheng Wang, Yueru Hou, Yanni Lin, Min Li, Liwei Xiao, Qingang Wu, Ying Meng, Guijun Liu, Shenghan Lou, Laishou Yang, Xueli Bai, Shengzhong Duan, Peng Zhan, Tong Liu, Zhimin Lu, Daqian Xu

{"title":"ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion","authors":"Yuran Duan, Zhiqiang Hu, Peng Han, Bo Lei, Shuo Wang, Zheng Wang, Yueru Hou, Yanni Lin, Min Li, Liwei Xiao, Qingang Wu, Ying Meng, Guijun Liu, Shenghan Lou, Laishou Yang, Xueli Bai, Shengzhong Duan, Peng Zhan, Tong Liu, Zhimin Lu, Daqian Xu","doi":"10.1038/s41556-025-01627-8","DOIUrl":"https://doi.org/10.1038/s41556-025-01627-8","url":null,"abstract":"<p>Highly aggressive tumours have evolved to restrain the cGAS–STING pathway for immune evasion, and the mechanisms underlying this hijacking remain unknown. Here we demonstrate that hypoxia induces robust STING activation in normal mammary epithelial cells but not in breast cancer cells. Mechanistically, adenylosuccinate lyase (ADSL), a key metabolic enzyme in de novo purine synthesis, is highly expressed in breast cancer tissues and is phosphorylated at T350 by hypoxia-activated IKKβ. Phosphorylated ADSL interacts with STING at the endoplasmic reticulum, where ADSL-produced fumarate binds to STING, leading to the inhibition of cGAMP binding to STING, STING activation and subsequent IRF3-dependent cytokine gene expression. Disrupting the ADSL–STING association promotes STING activation and blunts tumour growth. Notably, a combination treatment with ADSL endoplasmic reticulum translocation-blocking peptide and anti-PD-1 antibody induces an additive inhibitory effect on tumour growth accompanying a substantially increased immune response. Notably, ADSL T350 phosphorylation levels are inversely correlated with levels of STING activation and predicate poor prognosis in patients with breast cancer. These findings highlight a pivotal role of the metabolite fumarate in inhibiting STING activation and uncover new strategies to improve immune-checkpoint therapy by targeting ADSL-moonlighting function-mediated STING inhibition.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"9 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532308","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