Cell Death and Differentiation最新文献_第5页

Feeding cancer to death - a triad of aromatic acids reduces tumor growth 喂死癌症--三重芳香酸可减少肿瘤生长

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01372-9

Audrey Xavier, Ivan Dikic

引用次数: 0

The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation E3连接酶ASB3通过靶向泛素-蛋白酶体降解MAVS来下调抗病毒先天免疫能力

IF 12.4 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01376-5

Mingyang Cheng, Yiyuan Lu, Jiarui Wang, Haixu Wang, Yu Sun, Wenhui Zhao, Junhong Wang, Chunwei Shi, Jiawei Luo, Ming Gao, Tianxin Yu, Jianzhong Wang, Jiayao Guan, Nan Wang, Wentao Yang, Yanlong Jiang, Haibin Huang, Guilian Yang, Xin Cao, Dongqin Yang, Chunfeng Wang, Yan Zeng

{"title":"The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation","authors":"Mingyang Cheng, Yiyuan Lu, Jiarui Wang, Haixu Wang, Yu Sun, Wenhui Zhao, Junhong Wang, Chunwei Shi, Jiawei Luo, Ming Gao, Tianxin Yu, Jianzhong Wang, Jiayao Guan, Nan Wang, Wentao Yang, Yanlong Jiang, Haibin Huang, Guilian Yang, Xin Cao, Dongqin Yang, Chunfeng Wang, Yan Zeng","doi":"10.1038/s41418-024-01376-5","DOIUrl":"https://doi.org/10.1038/s41418-024-01376-5","url":null,"abstract":"E3 ubiquitin ligases are very important for regulating antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and IAV, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-β and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 presented decreased susceptibility to H9N2 and H1N1 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation of TBK1 and IRF3 and downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator that controls the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"6 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170875","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

Inhibition of nucleo-cytoplasmic proteasome translocation by the aromatic amino acids or silencing Sestrin3—their sensing mediator—is tumor suppressive 通过芳香族氨基酸抑制核-细胞质蛋白酶体转运或沉默Sestrin3--它们的感应介质--具有抑瘤作用

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01370-x

Ido Livneh, Bertrand Fabre, Gilad Goldhirsh, Chen Lulu, Adar Zinger, Yael Shammai Vainer, Maya Kaduri, Aviva Dahan, Tamar Ziv, Avi Schroeder, Yinon Ben-Neriah, Yaniv Zohar, Victoria Cohen-Kaplan, Aaron Ciechanover

{"title":"Inhibition of nucleo-cytoplasmic proteasome translocation by the aromatic amino acids or silencing Sestrin3—their sensing mediator—is tumor suppressive","authors":"Ido Livneh, Bertrand Fabre, Gilad Goldhirsh, Chen Lulu, Adar Zinger, Yael Shammai Vainer, Maya Kaduri, Aviva Dahan, Tamar Ziv, Avi Schroeder, Yinon Ben-Neriah, Yaniv Zohar, Victoria Cohen-Kaplan, Aaron Ciechanover","doi":"10.1038/s41418-024-01370-x","DOIUrl":"10.1038/s41418-024-01370-x","url":null,"abstract":"The proteasome, the catalytic arm of the ubiquitin system, is regulated via its dynamic compartmentation between the nucleus and the cytoplasm, among other mechanisms. Under amino acid shortage, the proteolytic complex is translocated to the cytoplasm, where it stimulates proteolysis to supplement recycled amino acids for essential protein synthesis. This response is mediated via the mTOR pathway and the lack of the three aromatic amino acids Tyr, Trp, and Phe (YWF). mTOR activation by supplementation of the triad inhibits proteasome translocation, leading to cell death. We now show that tumoral inherent stress conditions result in translocation of the proteasome from the nucleus to the cytosol. We further show that the modulation of the signaling cascade governed by YWF is applicable also to non-starved cells by using higher concentration of the triad to achieve a surplus relative to all other amino acids. Based on these two phenomena, we found that the modulation of stress signals via the administration of YWF leads to nuclear proteasome sequestration and inhibition of growth of xenograft, spontaneous, and metastatic mouse tumor models. In correlation with the observed effect of YWF on tumors, we found – using transcriptomic and proteomic analyses – that the triad affects various cellular processes related to cell proliferation, migration, and death. In addition, Sestrin3—a mediator of YWF sensing upstream of mTOR—is essential for proteasome translocation, and therefore plays a pro-tumorigenic role, positioning it as a potential oncogene. This newly identified approach for hijacking the cellular “satiety center” carries therefore potential therapeutic implications for cancer.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 10","pages":"1242-1254"},"PeriodicalIF":13.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01370-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170876","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

Correction: John F. R. Kerr (1934–2024) 更正：约翰-科尔（1934-2024）

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01373-8

Margaret C. Cummings, David L. Vaux, Andreas Strasser, Ruth Kluck

引用次数: 0

Intracellular zinc protects tumours from T cell-mediated cytotoxicity 细胞内锌可保护肿瘤免受 T 细胞介导的细胞毒性影响

IF 12.4 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-11 DOI: 10.1038/s41418-024-01369-4

Emily J. Lelliott, Jonathan Naddaf, Katherine Ganio, Jessica Michie, Shelly Wang, Lin Liu, Natasha Silke, Antonio Ahn, Kelly M. Ramsbottom, Amelia J. Brennan, Andrew J. Freeman, Shom Goel, Stephin J. Vervoort, Conor J. Kearney, Paul A. Beavis, Christopher A. McDevitt, John Silke, Jane Oliaro

{"title":"Intracellular zinc protects tumours from T cell-mediated cytotoxicity","authors":"Emily J. Lelliott, Jonathan Naddaf, Katherine Ganio, Jessica Michie, Shelly Wang, Lin Liu, Natasha Silke, Antonio Ahn, Kelly M. Ramsbottom, Amelia J. Brennan, Andrew J. Freeman, Shom Goel, Stephin J. Vervoort, Conor J. Kearney, Paul A. Beavis, Christopher A. McDevitt, John Silke, Jane Oliaro","doi":"10.1038/s41418-024-01369-4","DOIUrl":"https://doi.org/10.1038/s41418-024-01369-4","url":null,"abstract":"Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFβ) enhances tumour cell resistance to T cell killing, mediated through T cell-derived TNF. Mechanistically, RNA-sequencing and elemental analyses revealed that deletion of CBFβ disrupts numerous pathways including those involved in zinc homoeostasis. Moreover, we demonstrated that modulation of cellular zinc, achieved by supplementation or chelation, significantly altered tumour cell susceptibility to TNF by regulating the levels of inhibitor of apoptosis proteins. Consistent with this, treatment of tumour cells with a membrane-permeable zinc chelator had no impact on tumour cell viability alone, but significantly increased tumour cell lysis by CD8+ T cells in a TNF-dependent but perforin-independent manner. These results underscore the crucial role of intracellular zinc in regulating tumour cell susceptibility to T cell-mediated killing, revealing a novel vulnerability in tumour cells that might be exploited for the development of future cancer immunotherapeutics.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"28 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170461","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

Correction to: Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis 更正：两种热点突变 p53 小鼠模型在肿瘤发生过程中显示出不同的功能增益。

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-10 DOI: 10.1038/s41418-024-01366-7

W. Hanel, N. Marchenko, S. Xu, S. Xiaofeng Yu, W. Weng, U. Moll

引用次数: 0

PHGDH/SYK: a hub integrating anti-fungal immunity and serine metabolism PHGDH/SYK：整合抗真菌免疫和丝氨酸代谢的枢纽

IF 12.4 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-10 DOI: 10.1038/s41418-024-01374-7

Xinyong Zhang, Dongdong Hu, Xiaoyan Sun, Yichun Gu, Yong Zhou, Chuanxin Su, Shi Liu, Caiyan Zhang, Guoping Lu, Qiwen Wu, Aidong Chen

引用次数: 0

A chromosome-coupled ubiquitin-proteasome pathway is required for meiotic surveillance 减数分裂监控需要染色体偶联泛素-蛋白酶体途径

IF 12.4 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-05 DOI: 10.1038/s41418-024-01375-6

Ruirui Zhang, Bohan Liu, Yuqi Tian, Mingyu Xin, Qian Li, Xiuhua Huang, Yuanyuan Liu, Li Zhao, Feifei Qi, Ruoxi Wang, Xiaoqian Meng, Jianguo Chen, Jun Zhou, Jinmin Gao

{"title":"A chromosome-coupled ubiquitin-proteasome pathway is required for meiotic surveillance","authors":"Ruirui Zhang, Bohan Liu, Yuqi Tian, Mingyu Xin, Qian Li, Xiuhua Huang, Yuanyuan Liu, Li Zhao, Feifei Qi, Ruoxi Wang, Xiaoqian Meng, Jianguo Chen, Jun Zhou, Jinmin Gao","doi":"10.1038/s41418-024-01375-6","DOIUrl":"https://doi.org/10.1038/s41418-024-01375-6","url":null,"abstract":"Defects in meiotic prophase can cause meiotic chromosome missegregation and aneuploid gamete formation. Meiotic checkpoints are activated in germ cells with meiotic defects, and cells with unfixed errors are eliminated by apoptosis. How such a surveillance process is regulated remains elusive. Here, we report that a chromosome-coupled ubiquitin-proteasome pathway (UPP) regulates meiotic checkpoint activation and promotes germ cell apoptosis in C. elegans meiosis-defective mutants. We identified an F-box protein, FBXL-2, that functions as a core component within the pathway. This chromosome-coupled UPP regulates meiotic DSB repair kinetics and chromosome dynamic behaviors in synapsis defective mutants. Disrupted UPP impairs the axial recruitment of the HORMA domain protein HIM-3, which is required for efficient germ cell apoptosis in synapsis defective mutants. Our data suggest that an efficient chromosome-coupled UPP functions as a part of the meiotic surveillance system by enhancing the integrity of the meiotic chromosome axis.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"9 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137989","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

Foxk1 promotes bone formation through inducing aerobic glycolysis. Foxk1 通过诱导有氧糖酵解促进骨形成。

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-05 DOI: 10.1038/s41418-024-01371-w

Chungeng Liu, Naibo Feng, Zhenmin Wang, Kangyan Zheng, Yongheng Xie, Hongyu Wang, Houqing Long, Songlin Peng

{"title":"Foxk1 promotes bone formation through inducing aerobic glycolysis.","authors":"Chungeng Liu, Naibo Feng, Zhenmin Wang, Kangyan Zheng, Yongheng Xie, Hongyu Wang, Houqing Long, Songlin Peng","doi":"10.1038/s41418-024-01371-w","DOIUrl":"https://doi.org/10.1038/s41418-024-01371-w","url":null,"abstract":"Transcription factor Foxk1 can regulate cell proliferation, differentiation, metabolism, and promote skeletal muscle regeneration and cardiogenesis. However, the roles of Foxk1 in bone formation is unknown. Here, we found that Foxk1 expression decreased in the bone tissue of aged mice and osteoporosis patients. Knockdown of Foxk1 in primary murine calvarial osteoblasts suppressed osteoblast differentiation and proliferation. Conditional knockout of Foxk1 in preosteoblasts and mature osteoblasts in mice exhibited decreased bone mass and mechanical strength due to reduced bone formation. Mechanistically, we identified Foxk1 targeted the promoter region of many genes of glycolytic enzyme by CUT&Tag analysis. Lacking of Foxk1 in primary murine calvarial osteoblasts resulted in reducing aerobic glycolysis. Inhibition of glycolysis by 2DG hindered osteoblast differentiation and proliferation induced by Foxk1 overexpression. Finally, specific overexpression of Foxk1 in preosteoblasts, driven by a preosteoblast specific osterix promoter, increased bone mass and bone mechanical strength of aged mice, which could be suppressed by inhibiting glycolysis. In summary, these findings reveal that Foxk1 plays a vital role in the osteoblast metabolism regulation and bone formation stimulation, offering a promising approach for preventing age-related bone loss.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":" ","pages":""},"PeriodicalIF":13.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131921","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

Correction: Exosomal miR-101-3p and miR-423-5p inhibit medulloblastoma tumorigenesis through targeting FOXP4 and EZH2 更正：外泌体 miR-101-3p 和 miR-423-5p 通过靶向 FOXP4 和 EZH2 抑制髓母细胞瘤肿瘤发生。

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-04 DOI: 10.1038/s41418-024-01345-y

Ping Xue, Saihua Huang, Xiao Han, Caiyan Zhang, Lan Yang, Wenfeng Xiao, Jinrong Fu, Hao Li, Yufeng Zhou

引用次数: 0