EMBO Reports最新文献_第9页

Oncogenic YAP sensitizes cells to CHK1 inhibition via CDK4/6 driven G1 acceleration. 致癌YAP通过CDK4/6驱动的G1加速使细胞对CHK1抑制敏感。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-04 DOI: 10.1038/s44319-025-00514-5

Dörthe Gertzmann, Cornelius Presek, Anna Lena Mattes, Marco Sänger, Marie Zoller, Christina Schülein-Völk, Carsten P Ade, Martin Eilers, Stefan Gaubatz

{"title":"Oncogenic YAP sensitizes cells to CHK1 inhibition via CDK4/6 driven G1 acceleration.","authors":"Dörthe Gertzmann, Cornelius Presek, Anna Lena Mattes, Marco Sänger, Marie Zoller, Christina Schülein-Völk, Carsten P Ade, Martin Eilers, Stefan Gaubatz","doi":"10.1038/s44319-025-00514-5","DOIUrl":"10.1038/s44319-025-00514-5","url":null,"abstract":"Replication stress is a driver of genomic instability, contributing to carcinogenesis by causing DNA damage and mutations. While YAP, the downstream co-activator of the Hippo signaling pathway, plays a crucial role in regulating cell growth and differentiation, it is unclear whether it generates replication stress exploitable for therapy. Here, we report that oncogenic YAP shortens the G1 phase through increased CDK4/6 activity, leading to early S-phase entry. This causes origin underlicensing, an overall reduced rate of DNA replication, and, unusually, an accelerated speed of individual replication forks. CHK1 inhibition in cells expressing oncogenic YAP results in DNA damage during S-phase, which is not due to premature CDK1 activation or mitotic entry. Sensitivity to CHK1 inhibition depends on the YAP-TEAD interaction and involves a global increase in transcription and an increase in transcription-replication conflicts (TRCs). Replication stress from oncogenic YAP can be mitigated by restoring G1 length through partial CDK4/6 inhibition or by reducing YAP-induced hypertranscription. Our findings suggest a potential therapeutic strategy for targeting YAP-dependent cancers by exploiting their vulnerability to replication stress.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4017-4039"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564695","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

CLIPPERs - Clip the right protein - a new tool for targeted proteolysis in bacteria. CLIPPERs -夹住正确的蛋白质-细菌中靶向蛋白水解的新工具。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-25 DOI: 10.1038/s44319-025-00532-3

Marta Carroni

引用次数: 0

BRCA1 preserves genome integrity during the formation of undifferentiated spermatogonia. BRCA1在未分化精原细胞形成过程中保持了基因组的完整性。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-05-28 DOI: 10.1038/s44319-025-00487-5

Peng Li, Licun Song, Longfei Ma, Chunsheng Han, Lejun Li, Lin-Yu Lu, Yidan Liu

{"title":"BRCA1 preserves genome integrity during the formation of undifferentiated spermatogonia.","authors":"Peng Li, Licun Song, Longfei Ma, Chunsheng Han, Lejun Li, Lin-Yu Lu, Yidan Liu","doi":"10.1038/s44319-025-00487-5","DOIUrl":"10.1038/s44319-025-00487-5","url":null,"abstract":"Undifferentiated spermatogonia, which form shortly after birth, consist of spermatogonial stem cells and progenitor spermatogonia that maintain homeostasis. As the origin of spermatogenesis, undifferentiated spermatogonia must preserve genome integrity. Paradoxically, we demonstrate that massive spontaneous DNA damage, potentially generated by formaldehyde, arises during the formation of undifferentiated spermatogonia, posing a significant threat to genome integrity. We further reveal that BRCA1 is essential for the timely repair of this spontaneous DNA damage. BRCA1 loss leads to a dramatic reduction in progenitor spermatogonia and disrupts the formation of undifferentiated spermatogonia. Although spermatogonial stem cells initially undergo hyperproliferation, they are eventually depleted, resulting in the premature exhaustion of undifferentiated spermatogonia. Our study highlights a striking difference in DNA damage sensitivity between the two populations of undifferentiated spermatogonia and underscores the critical role of BRCA1-dependent DNA damage repair in preserving genome integrity during the formation of undifferentiated spermatogonia.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3747-3772"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173316","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

Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan. 分离肽聚糖的真菌抗菌内肽酶的鉴定。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-04 DOI: 10.1038/s44319-025-00508-3

Silke Machata, Ute Bertsche, Franziska Hoffmann, Zaher M Fattal, Franziska Kage, Michal Flak, Alexander N J Iliou, Falk Hillmann, Ferdinand von Eggeling, Hortense Slevogt, Axel A Brakhage, Ilse D Jacobsen

{"title":"Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan.","authors":"Silke Machata, Ute Bertsche, Franziska Hoffmann, Zaher M Fattal, Franziska Kage, Michal Flak, Alexander N J Iliou, Falk Hillmann, Ferdinand von Eggeling, Hortense Slevogt, Axel A Brakhage, Ilse D Jacobsen","doi":"10.1038/s44319-025-00508-3","DOIUrl":"10.1038/s44319-025-00508-3","url":null,"abstract":"Aspergillus fumigatus is a saprophytic fungus dwelling in soil and on decaying plant material, but also an opportunistic pathogen in immunocompromised patients. In its environmental niche, A. fumigatus faces competition from other microorganisms including bacteria. Here, we describe the discovery of the first secreted antibacterial protein in A. fumigatus. We identify a secreted fungal endopeptidase, designated CwhA, that cleaves peptidoglycan of Gram-positive bacteria at specific residues within the peptidoglycan stem peptide. Cleavage leads to bacterial lysis and the release of peptidoglycan cleavage products. Expression of cwhA is induced by the presence of bacteria. Furthermore, CwhA is highly abundant in murine lungs during invasive pulmonary aspergillosis and peptidoglycan cleavage products generated by CwhA stimulate cytokine production of human immune cells in vitro. Although CwhA does not affect human cells directly, this novel player in fungal-bacterial interactions could affect A. fumigatus infections by inhibiting Gram-positive bacteria in its vicinity, and possibly modulate the immune system.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3889-3916"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564692","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

NAT10-mediated acetylation of NIK mRNA in B cells promotes IgA production. nat10介导的B细胞NIK mRNA乙酰化促进了IgA的产生。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-04 DOI: 10.1038/s44319-025-00509-2

Wan-Jun Jiang, Xin-Tao Mao, Wen-Ping Li, Nicole Jin, Yu Wang, Guiping Guan, Jin Jin, Yi-Yuan Li

引用次数: 0

Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P. 免疫老化通过巨噬细胞来源的抗氧化硒蛋白P损害肌肉再生。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-18 DOI: 10.1038/s44319-025-00516-3

Dieu-Huong Hoang, Jessica Bouvière, Johanna Galvis, Pauline Moullé, Orane Mercier, Eugenia Migliavacca, Ananga Ghosh, Gaëtan Juban, Sophie Liot, Pascal Stuelsatz, Fabien Le Grand, Jérôme N Feige, Rémi Mounier, Bénédicte Chazaud

{"title":"Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P.","authors":"Dieu-Huong Hoang, Jessica Bouvière, Johanna Galvis, Pauline Moullé, Orane Mercier, Eugenia Migliavacca, Ananga Ghosh, Gaëtan Juban, Sophie Liot, Pascal Stuelsatz, Fabien Le Grand, Jérôme N Feige, Rémi Mounier, Bénédicte Chazaud","doi":"10.1038/s44319-025-00516-3","DOIUrl":"10.1038/s44319-025-00516-3","url":null,"abstract":"Muscle regeneration is impaired with aging, due to both intrinsic defects of muscle stem cells (MuSCs) and alterations of their niche. Here, we monitor the cells constituting the MuSC niche over time in young and old regenerating mouse muscle. Aging alters the expansion of all niche cells, with prominent phenotypes in macrophages that show impaired resolution of inflammation. RNA sequencing of FACS-isolated mononucleated cells uncovers specific profiles and kinetics of genes and molecular pathways in old versus young muscle cells, indicating that each cell type responds to aging in a specific manner. Moreover, we show that macrophages have an altered expression of Selenoprotein P (Sepp1). Macrophage-specific deletion of Sepp1 is sufficient to impair the acquisition of their restorative profile and causes inefficient skeletal muscle regeneration. When transplanted in aged mice, bone marrow from young WT mice, but not Sepp1-KOs, restores muscle regeneration. This work provides a unique resource to study MuSC niche aging, reveals that niche cell aging is asynchronous and establishes the antioxidant Selenoprotein P as a driver of age-related decline of muscle regeneration.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4153-4179"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667415","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

Student hostages in culture war. 文化战争中的学生人质。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-31 DOI: 10.1038/s44319-025-00527-0

Bernd Pulverer

引用次数: 0

Hippo pathway controls biopterin metabolism to shield adjacent cells from ferroptosis in lung cancer. Hippo通路控制生物蝶呤代谢以保护肺癌中邻近细胞免于铁下垂。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-07 DOI: 10.1038/s44319-025-00515-4

Hao Li, Yohei Kanamori, Akihiro Nita, Ayato Maeda, Tianli Zhang, Kenta Kikuchi, Hiroyuki Yamada, Touya Toyomoto, Mohamed Fathi Saleh, Mayumi Niimura, Hironori Hinokuma, Mayuko Shimoda, Koei Ikeda, Makoto Suzuki, Yoshihiro Komohara, Daisuke Kurotaki, Tomohiro Sawa, Toshiro Moroishi

{"title":"Hippo pathway controls biopterin metabolism to shield adjacent cells from ferroptosis in lung cancer.","authors":"Hao Li, Yohei Kanamori, Akihiro Nita, Ayato Maeda, Tianli Zhang, Kenta Kikuchi, Hiroyuki Yamada, Touya Toyomoto, Mohamed Fathi Saleh, Mayumi Niimura, Hironori Hinokuma, Mayuko Shimoda, Koei Ikeda, Makoto Suzuki, Yoshihiro Komohara, Daisuke Kurotaki, Tomohiro Sawa, Toshiro Moroishi","doi":"10.1038/s44319-025-00515-4","DOIUrl":"10.1038/s44319-025-00515-4","url":null,"abstract":"Recent advances in single-cell technologies have uncovered significant cellular diversity in tumors, influencing cancer progression and treatment outcomes. The Hippo pathway controls cell proliferation through its downstream effectors: yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). Our analysis of human lung adenocarcinoma and murine models revealed that cancer cells display heterogeneous YAP/TAZ activation levels within tumors. Murine lung cancer cells with high YAP/TAZ activity grow rapidly but are sensitive to ferroptosis, a cell death induced by lipid peroxidation. In contrast, cells with low YAP/TAZ activity grow slowly but resist ferroptosis. Moreover, they protect neighbouring cells from ferroptosis, creating a protective microenvironment that enhances the tumor's resistance to ferroptosis. Mechanistically, inhibiting YAP/TAZ upregulates GTP cyclohydrolase 1 (GCH1), an enzyme critical for the biosynthesis of tetrahydrobiopterin (BH4), which functions as a secretory antioxidant to prevent lipid peroxidation. Pharmacological inhibition of GCH1 sensitizes lung cancer cells to ferroptosis inducers, suggesting a potential therapeutic approach. Our data highlights the non-cell-autonomous roles of the Hippo pathway in creating a ferroptosis-resistant tumor microenvironment.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"4124-4152"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575075","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

Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males. 生长期饮食降低组蛋白乙酰转移酶Gcn5功能，缩短雄性果蝇寿命。

IF 6.2 1区生物学

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-07-10 DOI: 10.1038/s44319-025-00503-8

Shoko Mizutani, Kanji Furuya, Ayumi Mure, Yuuki Takahashi, Akihiro Mori, Nozomu Sakurai, Takuto Suito, Kohjiro Nagao, Masato Umeda, Kaori Watanabe, Yukako Hattori, Tadashi Uemura

{"title":"Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males.","authors":"Shoko Mizutani, Kanji Furuya, Ayumi Mure, Yuuki Takahashi, Akihiro Mori, Nozomu Sakurai, Takuto Suito, Kohjiro Nagao, Masato Umeda, Kaori Watanabe, Yukako Hattori, Tadashi Uemura","doi":"10.1038/s44319-025-00503-8","DOIUrl":"10.1038/s44319-025-00503-8","url":null,"abstract":"The nutritional environment in early life, referred to as the nutrition history, exerts far-reaching health effects beyond the developmental stage. Here, with Drosophila melanogaster as a model, we fed larvae on diets consisting of a variety of yeast mutants and explored the resulting histories that impacted adult lifespan. A larval diet comprised of yeast nat3 KO shortened the lifespan of male adults; and remarkably, this diet diminished the function of histone acetyltransferase Gcn5 in larvae. Concordantly, perturbation of Gcn5-mediated gene regulation in the larval whole body or neurons significantly contributed to the earlier death of adults. The nat3 KO diet is much more abundant in long-chain fatty acids and branched-chain amino acids (BCAAs) than the control yeast diet. Supplementing the control diet with a combination of oleic acid, valine, and acetic acid recapitulated the effects of the nat3 KO diet on the larval transcriptome and the lifespan of males. Our findings strongly suggest a causal link between a fatty acids- and BCAA-rich diet in developmental stages and lifespan reduction via the adverse effect on the Gcn5 function.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3856-3888"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607852","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

Palmitoylated importin α regulates mitotic spindle orientation through interaction with NuMA. 棕榈酰化输入蛋白α通过与NuMA相互作用调节有丝分裂纺锤体取向。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI: 10.1038/s44319-025-00484-8

Patrick James Sutton, Natalie Mosqueda, Christopher W Brownlee

{"title":"Palmitoylated importin α regulates mitotic spindle orientation through interaction with NuMA.","authors":"Patrick James Sutton, Natalie Mosqueda, Christopher W Brownlee","doi":"10.1038/s44319-025-00484-8","DOIUrl":"10.1038/s44319-025-00484-8","url":null,"abstract":"Regulation of cell division orientation is a fundamental process critical to differentiation and tissue homeostasis. Microtubules emanating from the mitotic spindle pole bind a conserved complex of proteins at the cell cortex which orients the spindle and ultimately the cell division plane. Control of spindle orientation is of particular importance in developing tissues, such as the developing brain. Misorientation of the mitotic spindle and thus subsequent division plane misalignment can contribute to improper segregation of cell fate determinants in developing neuroblasts, leading to a rare neurological disorder known as microcephaly. We demonstrate that the nuclear transport protein importin α, when palmitoylated, plays a critical role in mitotic spindle orientation through localizing factors, such as NuMA, to the cell cortex. We also observe craniofacial developmental defects in Xenopus laevis when importin α palmitoylation is abrogated, including smaller head and brains, a hallmark of spindle misorientation and microcephaly. These findings characterize not only a role for importin α in spindle orientation, but also a broader role for importin α palmitoylation which has significance for many cellular processes.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"3280-3304"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157325","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