EMBO Reports最新文献_第7页

Scientific truth: an endangered species. 科学真理：濒临灭绝的物种

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-24 DOI: 10.1038/s44319-024-00293-5

Frank Gannon

引用次数: 0

The controversy around anti-amyloid antibodies for treating Alzheimer's disease : The European Medical Agency's ruling against the latest anti-amyloid drugs highlights the ongoing debate about their safety and efficacy. 围绕用于治疗阿尔茨海默病的抗淀粉样蛋白抗体的争议：欧洲医学机构针对最新抗淀粉样蛋白药物的规定凸显了对其安全性和有效性的持续争论。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-23 DOI: 10.1038/s44319-024-00294-4

Philip Hunter

引用次数: 0

Targeting the transcription factor YY1 is synthetic lethal with loss of the histone demethylase KDM5C. 靶向转录因子 YY1 与组蛋白去甲基化酶 KDM5C 的缺失是合成致死的。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-21 DOI: 10.1038/s44319-024-00290-8

Qian Zheng, Pengfei Li, Yulong Qiang, Jiachen Fan, Yuzhu Xing, Ying Zhang, Fan Yang, Feng Li, Jie Xiong

{"title":"Targeting the transcription factor YY1 is synthetic lethal with loss of the histone demethylase KDM5C.","authors":"Qian Zheng, Pengfei Li, Yulong Qiang, Jiachen Fan, Yuzhu Xing, Ying Zhang, Fan Yang, Feng Li, Jie Xiong","doi":"10.1038/s44319-024-00290-8","DOIUrl":"https://doi.org/10.1038/s44319-024-00290-8","url":null,"abstract":"An understanding of the enzymatic and scaffolding functions of epigenetic modifiers is important for the development of epigenetic therapies for cancer. The H3K4me2/3 histone demethylase KDM5C has been shown to regulate transcription. The diverse roles of KDM5C are likely determined by its interacting partners, which are still largely unknown. In this study, we screen for KDM5C-binding proteins and show that YY1 interacts with KDM5C. A synergistic antitumor effect is exerted when both KDM5C and YY1 are depleted, and targeting YY1 appears to be a vulnerability in KDM5C-deficient cancer cells. Mechanistically, KDM5C promotes global YY1 chromatin recruitment, especially at promoters. Moreover, an intact KDM5C JmjC domain but not KDM5C histone demethylase activity is required for KDM5C-mediated YY1 chromatin binding. Transcriptional profiling reveals that dual inhibition of KDM5C and YY1 increases transcriptional repression of cell cycle- and apoptosis-related genes. In summary, our work demonstrates a synthetic lethal interaction between YY1 and KDM5C and suggests combination therapies for cancer treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460726","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

Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions. 谷氨酰胺、乳酸和甘油的糖生成和糖醛酸生成支持人体巨噬细胞的功能。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-18 DOI: 10.1038/s44319-024-00278-4

Najia Jeroundi, Charlotte Roy, Laetitia Basset, Pascale Pignon, Laurence Preisser, Simon Blanchard, Cinzia Bocca, Cyril Abadie, Julie Lalande, Naïg Gueguen, Guillaume Mabilleau, Guy Lenaers, Aurélie Moreau, Marie-Christine Copin, Guillaume Tcherkez, Yves Delneste, Dominique Couez, Pascale Jeannin

{"title":"Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions.","authors":"Najia Jeroundi, Charlotte Roy, Laetitia Basset, Pascale Pignon, Laurence Preisser, Simon Blanchard, Cinzia Bocca, Cyril Abadie, Julie Lalande, Naïg Gueguen, Guillaume Mabilleau, Guy Lenaers, Aurélie Moreau, Marie-Christine Copin, Guillaume Tcherkez, Yves Delneste, Dominique Couez, Pascale Jeannin","doi":"10.1038/s44319-024-00278-4","DOIUrl":"https://doi.org/10.1038/s44319-024-00278-4","url":null,"abstract":"Macrophages fight infection and ensure tissue repair, often operating at nutrient-poor wound sites. We investigated the ability of human macrophages to metabolize glycogen. We observed that the cytokines GM-CSF and M-CSF plus IL-4 induced glycogenesis and the accumulation of glycogen by monocyte-derived macrophages. Glyconeogenesis occurs in cells cultured in the presence of the inflammatory cytokines GM-CSF and IFNγ (M1 cells), via phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose-1,6-bisphosphatase 1 (FBP1). Enzyme inhibition with drugs or gene silencing techniques and 13C-tracing demonstrate that glutamine (metabolized by the TCA cycle), lactic acid, and glycerol were substrates of glyconeogenesis only in M1 cells. Tumor-associated macrophages (TAMs) also store glycogen and can perform glyconeogenesis. Finally, macrophage glycogenolysis and the pentose phosphate pathway (PPP) support cytokine secretion and phagocytosis regardless of the availability of extracellular glucose. Thus, glycogen metabolism supports the functions of human M1 and M2 cells, with inflammatory M1 cells displaying a possible dependence on glyconeogenesis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460724","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

RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer. RNA 结合蛋白 ZCCHC24 促进了三阴性乳腺癌的致瘤性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-17 DOI: 10.1038/s44319-024-00282-8

Yutaro Uchida, Ryota Kurimoto, Tomoki Chiba, Takahide Matsushima, Goshi Oda, Iichiroh Onishi, Yasuto Takeuchi, Noriko Gotoh, Hiroshi Asahara

{"title":"RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer.","authors":"Yutaro Uchida, Ryota Kurimoto, Tomoki Chiba, Takahide Matsushima, Goshi Oda, Iichiroh Onishi, Yasuto Takeuchi, Noriko Gotoh, Hiroshi Asahara","doi":"10.1038/s44319-024-00282-8","DOIUrl":"https://doi.org/10.1038/s44319-024-00282-8","url":null,"abstract":"Triple-negative breast cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival. Here, we identify the RNA-binding protein ZCCHC24 as enriched in the mesenchymal-like TNBC population. ZCCHC24 promotes the expression of a set of genes related to tumorigenicity and treatment resistance by directly binding to the cis-element \"UGUWHWWA\" in their mRNAs, thereby stabilizing them. One of the ZCCHC24 targets, ZEB1, is a transcription factor that promotes the expression of cancer stemness genes and reciprocally induces ZCCHC24 expression. ZCCHC24 knockdown by siRNAs shows a therapeutic effect and reduces the mesenchymal-like cell population in TNBC patient-derived xenografts. ZCCHC24 knockdown also has additive effects with the BET inhibitor JQ1 in suppressing tumor growth in TNBC patient-derived xenografts.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460725","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

Nup358 restricts ER-mitochondria connectivity by modulating mTORC2/Akt/GSK3β signalling. Nup358通过调节mTORC2/Akt/GSK3β信号限制ER-线粒体的连接。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-07-18 DOI: 10.1038/s44319-024-00204-8

Misha Kalarikkal, Rimpi Saikia, Lizanne Oliveira, Yashashree Bhorkar, Akshay Lonare, Pallavi Varshney, Prathamesh Dhamale, Amitabha Majumdar, Jomon Joseph

{"title":"Nup358 restricts ER-mitochondria connectivity by modulating mTORC2/Akt/GSK3β signalling.","authors":"Misha Kalarikkal, Rimpi Saikia, Lizanne Oliveira, Yashashree Bhorkar, Akshay Lonare, Pallavi Varshney, Prathamesh Dhamale, Amitabha Majumdar, Jomon Joseph","doi":"10.1038/s44319-024-00204-8","DOIUrl":"10.1038/s44319-024-00204-8","url":null,"abstract":"ER-mitochondria contact sites (ERMCSs) regulate processes, including calcium homoeostasis, energy metabolism and autophagy. Previously, it was shown that during growth factor signalling, mTORC2/Akt gets recruited to and stabilizes ERMCSs. Independent studies showed that GSK3β, a well-known Akt substrate, reduces ER-mitochondria connectivity by disrupting the VAPB-PTPIP51 tethering complex. However, the mechanisms that regulate ERMCSs are incompletely understood. Here we find that annulate lamellae (AL), relatively unexplored subdomains of ER enriched with a subset of nucleoporins, are present at ERMCSs. Depletion of Nup358, an AL-resident nucleoporin, results in enhanced mTORC2/Akt activation, GSK3β inhibition and increased ERMCSs. Depletion of Rictor, a mTORC2-specific subunit, or exogenous expression of GSK3β, was sufficient to reverse the ERMCS-phenotype in Nup358-deficient cells. We show that growth factor-mediated activation of mTORC2 requires the VAPB-PTPIP51 complex, whereas, Nup358's association with this tether restricts mTORC2/Akt signalling and ER-mitochondria connectivity. Expression of a Nup358 fragment that is sufficient for interaction with the VAPB-PTPIP51 complex suppresses mTORC2/Akt activation and disrupts ERMCSs. Collectively, our study uncovers a novel role for Nup358 in controlling ERMCSs by modulating the mTORC2/Akt/GSK3β axis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4226-4251"},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723245","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

Environmental DNA without borders : Let's embrace decentralised genomics to meet the UN's biodiversity targets. 环境 DNA 无国界：让我们拥抱分散的基因组学，实现联合国的生物多样性目标。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-25 DOI: 10.1038/s44319-024-00264-w

Maximilian R Stammnitz, Amber Hartman Scholz, David J Duffy

引用次数: 0

Cytoplasmic FBXO38 mediates PD-1 degradation. 细胞质中的 FBXO38 介导了 PD-1 的降解。

IF 5.3 1区生物学

EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-16 DOI: 10.1038/s44319-024-00254-y

Xiwei Liu, Xiangbo Meng, Zuomiao Lin, Shutan Jiang, Haifeng Liu, Shao-Cong Sun, Xiaolong Liu, Penghui Zhou, Xiaowu Huang, Lai Wei, Wei Yang, Chenqi Xu

引用次数: 0

Fat body glycolysis defects inhibit mTOR and promote distant muscle disorganization through TNF-α/egr and ImpL2 signaling in Drosophila larvae. 在果蝇幼虫体内，脂肪体糖酵解缺陷通过 TNF-α/egr 和 ImpL2 信号传导抑制 mTOR 并促进远端肌肉紊乱。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-09 DOI: 10.1038/s44319-024-00241-3

Miriam Rodríguez-Vázquez, Jennifer Falconi, Lisa Heron-Milhavet, Patrice Lassus, Charles Géminard, Alexandre Djiane

引用次数: 0

Epigenetic inheritance and gene expression regulation in early Drosophila embryos. 果蝇早期胚胎的表观遗传和基因表达调控。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-16 DOI: 10.1038/s44319-024-00245-z

Filippo Ciabrelli, Nazerke Atinbayeva, Attilio Pane, Nicola Iovino

{"title":"Epigenetic inheritance and gene expression regulation in early Drosophila embryos.","authors":"Filippo Ciabrelli, Nazerke Atinbayeva, Attilio Pane, Nicola Iovino","doi":"10.1038/s44319-024-00245-z","DOIUrl":"10.1038/s44319-024-00245-z","url":null,"abstract":"Precise spatiotemporal regulation of gene expression is of paramount importance for eukaryotic development. The maternal-to-zygotic transition (MZT) during early embryogenesis in Drosophila involves the gradual replacement of maternally contributed mRNAs and proteins by zygotic gene products. The zygotic genome is transcriptionally activated during the first 3 hours of development, in a process known as \"zygotic genome activation\" (ZGA), by the orchestrated activities of a few pioneer factors. Their decisive role during ZGA has been characterized in detail, whereas the contribution of chromatin factors to this process has been historically overlooked. In this review, we aim to summarize the current knowledge of how chromatin regulation impacts the first stages of Drosophila embryonic development. In particular, we will address the following questions: how chromatin factors affect ZGA and transcriptional silencing, and how genome architecture promotes the integration of these processes early during development. Remarkably, certain chromatin marks can be intergenerationally inherited, and their presence in the early embryo becomes critical for the regulation of gene expression at later stages. Finally, we speculate on the possible roles of these chromatin marks as carriers of epialleles during transgenerational epigenetic inheritance (TEI).","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4131-4152"},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282178","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