EMBO Reports最新文献

DSK2-mediated degradation of F-box protein LAO1 and class I TCPs modulates the nitrogen starvation response. dsk2介导的F-box蛋白la1和I类tcp的降解调节氮饥饿反应。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-30 DOI: 10.1038/s44319-025-00491-9

Yuanyuan Li, Shuyang Cheng, Xu Jin, Ruoxuan Wu, Yiyi Guo, Dezhi Wu, Jie Dong

{"title":"DSK2-mediated degradation of F-box protein LAO1 and class I TCPs modulates the nitrogen starvation response.","authors":"Yuanyuan Li, Shuyang Cheng, Xu Jin, Ruoxuan Wu, Yiyi Guo, Dezhi Wu, Jie Dong","doi":"10.1038/s44319-025-00491-9","DOIUrl":"https://doi.org/10.1038/s44319-025-00491-9","url":null,"abstract":"Plants have evolved intricate strategies to cope with various abiotic stresses. Ubiquitin-mediated protein degradation plays a key role in plant development as well as abiotic stress tolerance. In this study, we identify LAO1, an F-box protein with unknown function, as a negative regulator of plant fitness during nitrogen starvation. DOMINANT SUPPRESSOR OF KAR 2 (DSK2) interacts with and mediates the autophagic degradation of LAO1 protein during nitrogen starvation. The loss of LAO1 improves the fitness of an autophagy-deficient mutant, atg5-1, under nitrogen starvation. Intriguingly, mutations in DSK2 facilitate rather than reduce plant growth after nitrogen starvation. This unexpected effect of DSK2 knockout led us to discover that DSK2 also interacts with and degrades a group of class I TCP transcription factors. Phenotypic observations demonstrate that class I TCPs are crucial for plant adaptation to nitrogen starvation. Moreover, genetic analyses indicate that class I TCPs function downstream of LAO1 and counteract its negative effects. Collectively, our findings unveil a previously undescribed regulatory network governing plant fitness during nitrogen starvation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186773","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 conserved phage phosphoesterase enables evasion of bacterial antiviral immunity. 一种保守的噬菌体磷酸酯酶可以逃避细菌抗病毒免疫。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-29 DOI: 10.1038/s44319-025-00488-4

Junlong Li, Yihao Song, Xiao Guo, Zheng-Guo He

{"title":"A conserved phage phosphoesterase enables evasion of bacterial antiviral immunity.","authors":"Junlong Li, Yihao Song, Xiao Guo, Zheng-Guo He","doi":"10.1038/s44319-025-00488-4","DOIUrl":"https://doi.org/10.1038/s44319-025-00488-4","url":null,"abstract":"With the increasing prevalence of drug-resistant bacteria, antimicrobial resistance emerges as a global public health threat. Mycobacteriophages show exciting prospects for the treatment of drug-resistant bacterial infections. However, the molecular mechanism through which they escape host bacterial defenses remains unclear. Here, we report that the gene gp48 of the mycobacteriophage A10ZJ24, which encodes a metallophosphoesterase-like protein, is essential for killing Mycobacterium tuberculosis. Gp48 is expressed during early stages of phage infection, and the Gp48 protein efficiently disrupts mycobacterial genomic DNA integrity, thereby silencing the expression of multiple anti-phage defense genes. While gp48-deletion phages infect and inject their DNA normally into M. tuberculosis cells, they are not able to impair the activation of the bacterial anti-phage genes which inhibit the replication of the genomic DNA of the mutant phage. This study thus identifies a phage metallophosphoesterase as a novel tool for subverting host bacterial antiviral immunity and killing M. tuberculosis. Our work fills a critical gap in the current knowledge on the arms race between mycobacteriophages and M. tuberculosis.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180213","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

Author Correction: Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis. 作者更正：I类HDAC抑制剂增强YB-1乙酰化和氧化应激以阻止肉瘤转移。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-29 DOI: 10.1038/s44319-025-00478-6

Amal M El-Naggar, Syam Prakash Somasekharan, Yemin Wang, Hongwei Cheng, Gian Luca Negri, Melvin Pan, Xue Qi Wang, Alberto Delaidelli, Bo Rafn, Jordan Cran, Fan Zhang, Haifeng Zhang, Shane Colborne, Martin Gleave, Anna Mandinova, Nancy Kedersha, Christopher S Hughes, Didier Surdez, Olivier Delattre, Yuzhuo Wang, David G Huntsman, Gregg B Morin, Poul H Sorensen

引用次数: 0

KEAP1 retention in phase-separated p62 bodies drives liver damage under autophagy-deficient conditions. 在自噬缺陷条件下，相分离p62小体中KEAP1的保留会导致肝损伤。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-28 DOI: 10.1038/s44319-025-00483-9

Shuhei Takada, Nozomi Shinomiya, Gaoxin Mao, Hikaru Tsuchiya, Tomoaki Koga, Satoko Komatsu-Hirota, Yu-Shin Sou, Manabu Abe, Elena Ryzhii, Michitaka Suzuki, Mitsuyoshi Nakao, Satoshi Waguri, Hideaki Morishita, Masaaki Komatsu

{"title":"KEAP1 retention in phase-separated p62 bodies drives liver damage under autophagy-deficient conditions.","authors":"Shuhei Takada, Nozomi Shinomiya, Gaoxin Mao, Hikaru Tsuchiya, Tomoaki Koga, Satoko Komatsu-Hirota, Yu-Shin Sou, Manabu Abe, Elena Ryzhii, Michitaka Suzuki, Mitsuyoshi Nakao, Satoshi Waguri, Hideaki Morishita, Masaaki Komatsu","doi":"10.1038/s44319-025-00483-9","DOIUrl":"https://doi.org/10.1038/s44319-025-00483-9","url":null,"abstract":"Phase-separated p62 bodies activate NRF2, a key transcription factor for antioxidant response, by sequestering KEAP1, which targets NRF2 for degradation. Although p62 bodies containing KEAP1 are degraded by autophagy, they accumulate in various liver disorders. Their precise disease role remains unclear. We show that excessive KEAP1 retention in p62 bodies and NRF2 activation are major causes of liver damage when autophagy is impaired. In mice with weakened or blocked p62-KEAP1 interactions, KEAP1 retention and NRF2 activation under autophagy-deficient conditions were suppressed. Transcriptome and proteome analyses reveal that p62 mutants unable to bind KEAP1 normalize the expression of NRF2 targets induced by defective autophagy. Autophagy deficiency causes organelle accumulation, especially of the ER, regardless of p62 mutation. Liver damage and hepatomegaly resulting from autophagy suppression markedly improved in mice carrying p62 mutants, particularly those with blocked KEAP1 binding. These findings highlight excessive KEAP1 retention in p62 bodies and defective organelle turnover as key drivers of liver pathology, underscoring the significance of phase separation in vivo.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173357","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

Cancer microbiota: a focus on tumor-resident bacteria. 癌症微生物群：对肿瘤驻留细菌的关注。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-28 DOI: 10.1038/s44319-025-00482-w

Gerlanda Vella, Maria Rescigno

{"title":"Cancer microbiota: a focus on tumor-resident bacteria.","authors":"Gerlanda Vella, Maria Rescigno","doi":"10.1038/s44319-025-00482-w","DOIUrl":"https://doi.org/10.1038/s44319-025-00482-w","url":null,"abstract":"Accumulating evidence highlights the presence of an intratumoral microbiota across various cancer types. Among all the microorganisms comprising the tumor-associated microbiota, tumor-resident bacteria (TRB) are increasingly recognized as critical regulators of cancer biology. Within tumor tissues, these microorganisms interact with various components of the tumor microenvironment (TME) and influence both tumor-promoting and tumor-suppressing pathways, underlying their dual role in cancer. Fully understanding the functional roles of TRB and their complex interactions with components of the TME requires the application of multimodal technologies. Developing strategies to modulate TRB-either by eradicating pathogenic populations or harnessing beneficial ones-holds great promise for advancing cancer treatment. In this review, we summarize the most recent insights into TRB. We discuss their possible origins and their implications on cancer biology, focusing on their roles in cancer development, metastasis establishment, immune modulation, and therapy response. Finally, we describe bacteria-based strategies and address the major challenges in detecting and analyzing these microbial communities in tumors.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173351","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

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 6.5 1区生物学

EMBO Reports Pub 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":"https://doi.org/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":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2025-05-27 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":"https://doi.org/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":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Articulating the need to minimize moral incursions in research : The least infringement condition. 阐明研究中道德侵害最小化的必要性：最小侵害条件。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-27 DOI: 10.1038/s44319-025-00490-w

Jeremy Sugarman

引用次数: 0

Elevated TGF-β1 impairs synaptic and cognitive function through activation of Smad2/3-Sp1 pathway in AngII-related hypertension. 升高的TGF-β1通过激活Smad2/3-Sp1通路在血管相关性高血压中损害突触和认知功能。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-27 DOI: 10.1038/s44319-025-00470-0

Cuiping Guo, Wensheng Li, Yuanyuan Li, Yi Liu, Yacoubou Abdoul Razak Mahaman, Jianzhi Wang, Hongbin Luo, Rong Liu, Hui Shen, Xiaochuan Wang

{"title":"Elevated TGF-β1 impairs synaptic and cognitive function through activation of Smad2/3-Sp1 pathway in AngII-related hypertension.","authors":"Cuiping Guo, Wensheng Li, Yuanyuan Li, Yi Liu, Yacoubou Abdoul Razak Mahaman, Jianzhi Wang, Hongbin Luo, Rong Liu, Hui Shen, Xiaochuan Wang","doi":"10.1038/s44319-025-00470-0","DOIUrl":"https://doi.org/10.1038/s44319-025-00470-0","url":null,"abstract":"Vascular dementia (VaD) is characterized by cognitive decline due to reduced cerebral blood flow, although its molecular mechanisms remain unclear. This study shows that angiotensin II (AngII) elevates blood pressure, reduces hippocampal blood flow, and impairs synaptic and cognitive function, which correlates with increased TGF-β1 levels. Overexpressing TGF-β1 in rats induces similar deficits, while its downregulation partially mitigates these effects, with the exception of hypoperfusion. Phosphorylation of Smad2/3, downstream of TGF-β1, is elevated in AngII-treated rats and TGF-β1-exposed neurons, and inhibiting Smad2/3 activation prevents synaptic damage. Additionally, phosphorylated Smad2/3 interacts more with the transcription factor Sp1 in hippocampal neurons of AngII-treated rats. Overexpression of Sp1 worsens synaptic and cognitive function, whereas Sp1 knockdown improves TGF-β1-induced impairments. These findings highlight TGF-β1 as a key mediator of AngII-induced cognitive deficits, beyond hypoperfusion, suggesting that targeting the TGF-β1/Smad2/3/Sp1 axis may offer therapeutic benefits for hypertension-related synaptic and cognitive dysfunction.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157322","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

LRRK2 interactions with microtubules are independent of LRRK2-mediated Rab phosphorylation. LRRK2与微管的相互作用不依赖于LRRK2介导的Rab磷酸化。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-05-27 DOI: 10.1038/s44319-025-00486-6

Tuyana Malankhanova, Zhiyong Liu, Enquan Xu, Nicole Bryant, Ki Woon Sung, Huizhong Li, Samuel Strader, Andrew B West

{"title":"LRRK2 interactions with microtubules are independent of LRRK2-mediated Rab phosphorylation.","authors":"Tuyana Malankhanova, Zhiyong Liu, Enquan Xu, Nicole Bryant, Ki Woon Sung, Huizhong Li, Samuel Strader, Andrew B West","doi":"10.1038/s44319-025-00486-6","DOIUrl":"https://doi.org/10.1038/s44319-025-00486-6","url":null,"abstract":"Deregulated microtubules are common defects associated with neurodegenerative diseases. Recent cryo-electron microscopy studies in cell lines overexpressing Parkinson's disease-associated LRRK2 suggest microtubule surfaces may regulate kinase activity by stabilizing different LRRK2 conformations. In macrophages with high endogenous LRRK2 expression, we find that nocodazole treatment destabilizes microtubules and impairs LRRK2-mediated Rab phosphorylation. GTP supplementation restores nocodazole-reduced Rab phosphorylation, linking LRRK2 kinase action to cellular GTP levels. Chemical microtubule stabilization, and kinetically trapping LRRK2 to microtubule surfaces, has negligible effects on Rab phosphorylation. In contrast, trapping LRRK2 to LAMP1-positive membranes upregulates LRRK2-mediated Rab phosphorylation. Proximity-labeling proteomics and colocalization studies show that LRRK2 robustly interacts with both polymerized and free tubulin transiently and independently of LRRK2 kinase activity. Endogenous LRRK2 complexed with type I inhibitors in neurons and macrophages fails to stably interact with microtubules, whereas bulky N-terminal tags fused to LRRK2 promotes stable microtubule binding in cell lines. Collectively, these results show that tubulin isoforms and microtubules are transient LRRK2-interacting proteins non-essential for LRRK2-mediated Rab phosphorylation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157323","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