The FEBS journal最新文献_第7页

ICAM-1 mediated inhibition of microglial inflammation through ERK/STAT3 signalling pathway improves cognitive functions in 5xFAD mouse model of Alzheimer's disease ICAM-1通过ERK/STAT3信号通路介导的小胶质细胞炎症抑制改善老年痴呆症5xFAD小鼠模型的认知功能。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-05-04 DOI: 10.1111/febs.70531

Soumita Goswami, Nimai Gorai, Subhas Chandra Biswas

{"title":"ICAM-1 mediated inhibition of microglial inflammation through ERK/STAT3 signalling pathway improves cognitive functions in 5xFAD mouse model of Alzheimer's disease","authors":"Soumita Goswami, Nimai Gorai, Subhas Chandra Biswas","doi":"10.1111/febs.70531","DOIUrl":"10.1111/febs.70531","url":null,"abstract":"Microgliosis is one of the early hallmarks of Alzheimer's disease (AD) that plays a crucial role in disease pathogenesis. Microglia play a defensive role by phagocytosing and clearing amyloid-β (Aβ) aggregates. However, excessive uptake of Aβ leads to impairment of its clearing ability, which results in neuroinflammation and eventually neurodegeneration. Thus, enhancing microglial phagocytosis and reducing its pro-inflammatory functions are promising strategies for AD therapy. However, harnessing microglial activation for long-term benefits in controlling disease pathogenesis in AD is currently lacking. Our recent findings revealed that the astrocyte secreted cytokine Intercellular adhesion molecule 1 (ICAM-1) improves memory and cognitive impairments in a 5xFAD mouse model of AD. Here, we investigated the involvement of microglia in ICAM-1 function since its receptor, LFA-1, is expressed in microglia. We found that ICAM-1 blocks Aβ-mediated microglial inflammatory activation by inhibiting the ERK-STAT3 pathway, which is indispensable for microglial inflammation. Further, we found that ICAM-1 potentiates microglial phagocytic ability to eliminate Aβ in primary culture. Additionally, ICAM-1 reduced Aβ plaque load and associated microglial reactivation in the 5xFAD mouse hippocampus. This reduction in plaque-associated microgliosis led to improved synaptic protein expressions which was reflected in significant cognitive improvement. Moreover, blocking the binding between ICAM-1 with its receptor LFA-1 partially reduced ICAM-1-mediated microglial modification. Collectively, these findings suggest that ICAM-1 plays a pivotal role in modifying microglial phagocytic and inflammatory functions via the ERK-STAT3 signalling pathway, thereby contributing to Aβ clearance and cognitive improvements.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5922-5951"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oligomeric defects in soybean serine hydroxymethyltransferase 8: tetramer destabilization by A149T and other variants associated with soybean cyst nematode resistance 大豆丝氨酸羟甲基转移酶8的低聚体缺陷：A149T和其他与大豆囊肿线虫抗性相关的变异体的四聚体不稳定。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-03-31 DOI: 10.1111/febs.70528

Vindya Samarakoon, David P. Buckley, Luckio F. Owuocha, Clarissa L. Durie, Melissa G. Mitchum, Lesa J. Beamer

{"title":"Oligomeric defects in soybean serine hydroxymethyltransferase 8: tetramer destabilization by A149T and other variants associated with soybean cyst nematode resistance","authors":"Vindya Samarakoon, David P. Buckley, Luckio F. Owuocha, Clarissa L. Durie, Melissa G. Mitchum, Lesa J. Beamer","doi":"10.1111/febs.70528","DOIUrl":"10.1111/febs.70528","url":null,"abstract":"Serine hydroxymethyltransferase (SHMT) is a conserved enzyme in folate-mediated one-carbon metabolism, where it contributes to nucleotide biosynthesis, methylation capacity, and cellular stress responses. Amino acid polymorphisms of soybean SHMT8 are known to affect the resistance of soybean to its primary pathogen, the soybean cyst nematode (SCN). A set of SHMT8 variants from ethyl methanesulfonate (EMS)-mutagenized soybean populations has been identified with varying resistance phenotypes, but their biochemical consequences remain poorly understood. Here, we use biochemical and structural studies to assess the impacts of the A149T variant on soybean SHMT8. Despite the conservative nature of the substitution, A149T reduces folate binding, pyridoxal-5′-phosphate–dependent catalysis, and thermal stability. High-resolution crystal structures (1.9–2.3 Å resolution) reveal only very minor structural changes. However, while the usual tetrameric assembly of the enzyme is retained at the high protein concentration in crystals, multiple other methods including a 2.9 Å cryo-electron microscopy (cryo-EM) structure show that the A149T variant is predominantly a dimer. Significant structural changes in the dimer are consistent with the observed biochemical impacts of the variant and help explain the well-known reduction in activity associated with dimerization of SHMT in other systems. We also find destabilization of the tetrameric assembly in other SHMT8 variants associated with changes in SCN resistance, suggesting that weakened oligomerization may be a common consequence of such mutations. Together, these results highlight quaternary structure as a critical determinant of SHMT8 activity and stability and suggest a potential mechanistic link between enzyme biochemistry and soybean defense.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5780-5800"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The R203W substitution drives PACS-1 syndrome by disrupting intramolecular regulation R203W替代通过破坏分子内调控驱动PACS-1综合征。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-03-20 DOI: 10.1111/febs.70492

Troy C. Krzysiak, In-Ja L. Byeon, Ryan Ponticelli, Mary E. Lucas, Lariah Thompson, Christopher DeHaven, Gary Thomas, Angela M. Gronenborn

{"title":"The R203W substitution drives PACS-1 syndrome by disrupting intramolecular regulation","authors":"Troy C. Krzysiak, In-Ja L. Byeon, Ryan Ponticelli, Mary E. Lucas, Lariah Thompson, Christopher DeHaven, Gary Thomas, Angela M. Gronenborn","doi":"10.1111/febs.70492","DOIUrl":"10.1111/febs.70492","url":null,"abstract":"The c607C>T mutation in the PACS1 gene results in an Arg203Trp substitution in the multifunctional protein PACS-1, and drives a syndrome characterized by intellectual disability, seizures, craniofacial dysmorphisms, and various characteristics of the autism spectrum. On the molecular level, this syndrome, in part, results from enhanced association of PACS-1 with the protein deacetylase HDAC6. PACS-1 uses its Furin binding region (FBR: amino acids 101–273) to directly interact with the catalytic domains of HDAC6. We present the solution structure of a chimeric PACS-1 FBR and use NMR to demonstrate that the PACS-1/HDAC6 interaction is regulated by an intramolecular mechanism involving the central unstructured region of PACS-1 folding back across the FBR and engaging in contacts with an extended, positively charged loop. The R203W substitution, located in this loop, disrupts this regulatory interaction and, in vitro, displays the ability to promote aberrant protein–protein interactions.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5717-5734"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147489142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coiled-coil centrosomal proteins facilitate tubulin concentration via polyKR motifs 盘绕状中心体蛋白通过多基序促进微管蛋白浓度。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-04-03 DOI: 10.1111/febs.70533

Shiou-Lan Lin, Yu-Hsun Chen, Ren Jun Loi, Yueh-Ting Chen, Ting Chen, Karine Lapouge, Garrett Greenan, Hans-Georg Kräusslich, Hui-Chun Cheng

{"title":"Coiled-coil centrosomal proteins facilitate tubulin concentration via polyKR motifs","authors":"Shiou-Lan Lin, Yu-Hsun Chen, Ren Jun Loi, Yueh-Ting Chen, Ting Chen, Karine Lapouge, Garrett Greenan, Hans-Georg Kräusslich, Hui-Chun Cheng","doi":"10.1111/febs.70533","DOIUrl":"10.1111/febs.70533","url":null,"abstract":"Centrosomes organize microtubules (MT) in animal cells by recruiting a group of MT polymerization factors to the pericentriolar matrix (PCM). Tubulin enrichment within the PCM contributes to microtubule-organizing activity. However, the molecular determinants underlying this tubulin concentration remain elusive. Here, we describe a mechanism of tubulin concentration by polyKR motifs encoded in the centrosomal coiled-coil proteins. We show that polyKR sequences promote tubulin enrichment within engineered protein condensates that mimic the protein-dense environment of the centrosome. Bioinformatic analysis reveals that polyKR motif-containing coiled-coil proteins are highly enriched in centrosomes across species, from worms and flies to mice and humans. The tubulin binding affinity of polyKR motifs with six to 10 basic residues is approximately in the micromolar to submicromolar range. Cytoplasmic puncta containing the predicted centrosomal polyKR motifs concentrate microtubules. In purified systems, we show that TACC3 and Cep63 condensates containing polyKR motifs concentrate tubulin dimers over 10-fold. Moreover, the spatial density of polyKR motifs correlates with MT concentration, suggesting that cells can modulate tubulin concentration at the PCM by tuning the centrosomal composition. Our findings highlight a general function encoded in centrosomal scaffolding proteins for tubulin concentration, and this mechanism is functionally redundant to ensure robust tubulin enrichment in the PCM.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5801-5813"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The nuts-and-bolts of ribosomal protein s6 kinase 1 regulation: A shared responsibility for mTOR complexes 1 and 2 核糖体蛋白s6激酶1调控的具体细节：mTOR复合物1和2的共同责任。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-06-05 DOI: 10.1111/febs.70612

Sheikh Tahir Majeed, Rabiya Majeed, Khurshid I. Andrabi

{"title":"The nuts-and-bolts of ribosomal protein s6 kinase 1 regulation: A shared responsibility for mTOR complexes 1 and 2","authors":"Sheikh Tahir Majeed, Rabiya Majeed, Khurshid I. Andrabi","doi":"10.1111/febs.70612","DOIUrl":"10.1111/febs.70612","url":null,"abstract":"Ribosomal protein S6 kinase 1 (S6K1) is a master regulator of cell growth and metabolism and a primary effector of the mTOR signaling pathway. Given its central role in cancer and metabolic diseases, S6K1 is a high-priority therapeutic target; however, developing effective treatments requires a definitive understanding of how the enzyme is activated. This review provides a comprehensive synthesis of S6K1 biology, covering its structural domains, various chemical modifications like acetylation and ubiquitination, and its regulation by noncoding RNAs. We specifically highlight the transition from traditional ‘canonical’ models to an emerging ‘non-canonical’ paradigm. Central to this shift is the proposal that S6K1 activation is a shared responsibility between two complexes: mTORC1 and mTORC2. We detail a two-step mechanism where mTORC1 first ‘primes’ the enzyme by relieving internal constraints, allowing mTORC2 to complete the activation process. By reconciling these different models and addressing long-standing questions about drug sensitivity, this review establishes a modern framework for S6K1 biology and identifies new opportunities for precise therapeutic intervention.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5669-5685"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying targeting signals and distinct localization-based roles of yeast aldehyde dehydrogenase Hfd1 酵母醛脱氢酶Hfd1的靶向信号及定位作用

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-04-07 DOI: 10.1111/febs.70536

Yuta Konishi, Haruka Sakaue, Hironori Takeda, Toshiya Endo

引用次数: 0

Determination of the water network surrounding the type I pilus from Escherichia coli by cryo-electron microscopy 低温电镜法测定大肠杆菌I型菌毛周围的水网。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-02-24 DOI: 10.1111/febs.70473

Tatiana E. Petrova, Anatoly S. Glukhov, Artem Stetsenko, Albert Guskov, Azat G. Gabdulkhakov

{"title":"Determination of the water network surrounding the type I pilus from Escherichia coli by cryo-electron microscopy","authors":"Tatiana E. Petrova, Anatoly S. Glukhov, Artem Stetsenko, Albert Guskov, Azat G. Gabdulkhakov","doi":"10.1111/febs.70473","DOIUrl":"10.1111/febs.70473","url":null,"abstract":"Type 1 pili are protein filamentous surface structures of Gram-negative bacteria that mediate adhesion to host and play a crucial role in infection. Here, we report the cryogenic electron microscopy structure of the type 1 pilus from E. coli K-12 comprising 15 subunits of the major protein pilin FimA. The final local resolution of electron microscopy reconstruction was estimated to reach 1.85 Å, which is higher than that of the previously published structure. This improvement in the resolution enabled us to refine side-chain conformations to reliably determine the distances between the side-chain residues participating in the intersubunit interactions and determine a network of water molecules surrounding the pilus rod. The analysis revealed that water contributes to intersubunit stabilization both through discrete bridging interactions and through extended hydrogen-bonded clusters, thereby supporting both the rigidity and flexibility of the filament. Comparison with a homologous high-resolution pilus model from enterotoxigenic E. coli showed that the vast majority of ‘conserved’ water molecules, that is, those that are present at equivalent positions in different subunits of our model occupy also equivalent positions across the two structures, underscoring their functional relevance. At the same time, sequence-specific differences in hydration patterns were observed. These findings highlight the structural and functional importance of water in pilus architecture and provide a more detailed molecular framework for understanding bacterial adhesion.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5703-5716"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Water, water, every where—the advent of hydrated pili structure 水，水，无处不在——水合菌毛结构的出现。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-04-25 DOI: 10.1111/febs.70551

Hiroya Oki, Hideki Shigematsu, Kazuki Kawahara, Christoph Gerle

引用次数: 0

The H19/miR-760/BST2 regulatory axis sustains breast cancer tumorigenesis and metastasis. H19/miR-760/BST2调控轴维持乳腺癌的肿瘤发生和转移。

IF 4.2

The FEBS journal Pub Date : 2026-09-30 DOI: 10.1111/febs.70746

Kekely Klouyovo, Evodie Peperstraete, Léa Mabille, Joséphine Louvieaux, Jim Marmuse, Clément Lecerf, Chann Lagadec, Xuefen Le Bourhis, Éric Adriaenssens

{"title":"The H19/miR-760/BST2 regulatory axis sustains breast cancer tumorigenesis and metastasis.","authors":"Kekely Klouyovo, Evodie Peperstraete, Léa Mabille, Joséphine Louvieaux, Jim Marmuse, Clément Lecerf, Chann Lagadec, Xuefen Le Bourhis, Éric Adriaenssens","doi":"10.1111/febs.70746","DOIUrl":"https://doi.org/10.1111/febs.70746","url":null,"abstract":"The long noncoding RNA H19 has been widely attested as a promoter of breast cancer by favoring proliferation, migration, invasion, and tumor growth. In this study, we attempted to decipher molecular mechanisms underlying oncogenic activities of H19. Transcriptomic analyses revealed that H19 overexpression correlates with increased BST2 expression at both transcriptional and protein levels in breast cancer cell lines. Functional assays demonstrated that BST2 overexpression mimics H19 oncogenic effects by enhancing tumor cell aggressiveness in vitro and tumor growth in vivo. Interestingly, we also observed a reciprocal regulation, where BST2 expression modulates H19 levels, suggesting a cross-regulatory mechanism. Further mechanistic studies identified miR-760 as a key post-transcriptional regulator orchestrating this interplay. Using luciferase reporter assays and miRNA modulation strategies, we found that miR-760 directly targets both H19 and BST2, thereby regulating their expression in a coordinated manner. Our findings uncover a novel H19/miR-760/BST2 regulatory axis that enhances breast cancer progression and suggest that this axis could be studied to identify potential targets for therapeutic intervention.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improving the differentiation capability of porcine induced pluripotent stem cells by using the additional reprogramming factor TBX3. 利用附加重编程因子TBX3提高猪多能干细胞的分化能力。

IF 4.2

The FEBS journal Pub Date : 2026-09-30 DOI: 10.1111/febs.70733

Yu-Jing Liao, Jenn-Rong Yang, Hsiao-Yun Kuo, Yi-Shiou Chen, Yu-Ching Lin, Shrikesh Sachdev, Dae-Young Kim, R Michael Roberts, Ye Yuan, Toshihiko Ezashi

{"title":"Improving the differentiation capability of porcine induced pluripotent stem cells by using the additional reprogramming factor TBX3.","authors":"Yu-Jing Liao, Jenn-Rong Yang, Hsiao-Yun Kuo, Yi-Shiou Chen, Yu-Ching Lin, Shrikesh Sachdev, Dae-Young Kim, R Michael Roberts, Ye Yuan, Toshihiko Ezashi","doi":"10.1111/febs.70733","DOIUrl":"https://doi.org/10.1111/febs.70733","url":null,"abstract":"Porcine induced pluripotent stem cells (piPSCs) generated via standard reprogramming factors typically remain dependent on exogenous transgene expression to maintain pluripotency and exhibit limited differentiation potential. Improving these limitations is essential for both regenerative medicine and agricultural biotechnology. To enhance the quality of piPSCs, we introduced an episomal plasmid encoding TBX3 in addition to the standard reprogramming factors with transgene-free piPSC lines established via WNT pathway inhibition. Furthermore, we developed optimized differentiation protocols to efficiently generate smooth muscle cells (SMCs), endothelial cells (ECs), hepatocyte-like cells (HLCs), and cardiomyocytes from piPSCs. TBX3-reprogrammed piPSCs (TBX3-piPSC) expressed both SSEA-1 and SSEA-4 surface markers, in contrast to standard piPSCs, which expressed only SSEA-1. TBX3-piPSC rapidly silenced exogenous reprogramming factors and formed teratomas containing well-differentiated tissues from all three germ layers. In contrast, standard piPSCs formed poorly differentiated teratomas composed mainly of mesenchymal and neuroectodermal tissues, consistent with previous reports of transgene-dependent piPSCs. TBX3-piPSC also formed embryoid bodies that demonstrated broader differentiation capacity. Under directed differentiation conditions, TBX3-piPSC efficiently gave rise to SMCs, ECs, HLCs, and beating cardiomyocytes. Thus, we conclude that the addition of TBX3 as a reprogramming factor promotes the generation of transgene-free piPSCs with enhanced differentiation potential. These findings provide a significant advancement in porcine stem cell biology and expand the potential applications of piPSCs.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0