FEBS Letters最新文献_第3页

Asymmetry in ubiquitin binding by A20 reveals early recognition features of the ubiquitin code. A20与泛素结合的不对称性揭示了泛素编码的早期识别特征。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 DOI: 10.1002/1873-3468.70337

Erik Walinda, Julia Rose McCarthy-Page, Kazuhiro Iwai, Daichi Morimoto

{"title":"Asymmetry in ubiquitin binding by A20 reveals early recognition features of the ubiquitin code.","authors":"Erik Walinda, Julia Rose McCarthy-Page, Kazuhiro Iwai, Daichi Morimoto","doi":"10.1002/1873-3468.70337","DOIUrl":"https://doi.org/10.1002/1873-3468.70337","url":null,"abstract":"<p><p>Linear (Met1-linked) polyubiquitin chains play essential roles in NF-κB signaling, with readers such as A20 specifically recognizing these chains via specialized domains. Although structural data exist for the linear diubiquitin-A20 ZF7 complex, the basis for its strong preference for linear polyubiquitin remains unclear. Here, we investigated the early steps of ubiquitin recognition by A20-ZF7, identifying that A20-ZF7 exhibits weak binding to monoubiquitin and distinct exchange kinetics at its two ubiquitin-binding sites, with slow exchange at the proximal site reflecting stronger binding. Comparison of monoubiquitin and linear diubiquitin binding suggested a multistep mechanism involving a kinetically resolvable intermediate state absent in the monoubiquitin interaction. This intermediate likely facilitates proper ubiquitin chain positioning and contributes to A20-ZF7's specificity for linear polyubiquitin. Impact statement We reveal transient intermediate states in ubiquitin recognition by A20 ZF7, showing that specificity for linear chains arises from a multistep kinetic pathway. This work highlights the importance of dynamic binding processes in decoding ubiquitin signaling.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Glucose intolerance induced by early estrogen deprivation and fructose-rich diet does not impair heart function in female rodents 早期雌激素剥夺和富含果糖饮食诱导的葡萄糖耐受不良对雌性啮齿动物的心脏功能没有损害。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2025-11-26 DOI: 10.1002/1873-3468.70235

Alonzo Illanes, Gustavo J. Monzón, Rocio García, Marilen Federico, Juan Lofeudo, Enrique Leo Portiansky, Silvia López-Morán, Mónica E. Rando, Adriana Grismaldo, Cecilia E. Corne, Maria Cecilia Castro, Paula G. Blanco, María Celeste Villa-Abrille, Julieta Palomeque

{"title":"Glucose intolerance induced by early estrogen deprivation and fructose-rich diet does not impair heart function in female rodents","authors":"Alonzo Illanes, Gustavo J. Monzón, Rocio García, Marilen Federico, Juan Lofeudo, Enrique Leo Portiansky, Silvia López-Morán, Mónica E. Rando, Adriana Grismaldo, Cecilia E. Corne, Maria Cecilia Castro, Paula G. Blanco, María Celeste Villa-Abrille, Julieta Palomeque","doi":"10.1002/1873-3468.70235","DOIUrl":"10.1002/1873-3468.70235","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>It was previously shown that a fructose-rich diet (FRD) induces prediabetes, cardiac dysfunction, and hypertrophy (CH) in males. We assessed FRD and estrogen depletion on female metabolism and cardiovascular function. Females on FRD or control diet (CD) did not develop prediabetes or cardiac dysfunction, although FRD-fed mice showed CH vs. CD. One month of ovariectomy (OVX) did not induce prediabetes, but FRD impaired glucose tolerance in OVX mice without additional metabolic or cardiac changes. Calcium transient amplitude decreased in OVX-FRD vs. SHAM-FRD, with delayed decay, suggesting reduced activity of the sarcoplasmic/endoplasmic reticulum Ca<sup>2+</sup> ATPase (SERCA2a). Sodium-hydrogen exchanger 1 (NHE1) expression also decreased in OVX–FRD. These findings indicate estrogen loss does not cause dysfunction but modifies glycemic response to FRD, while reduced NHE1 may help preserve cardiac function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 \u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>In ovariectomized (OVX) mice, estrogen deficiency leads to insulin resistance and impaired glucose tolerance only when combined with a fructose-rich diet (FRD); neither OVX nor FRD alone is sufficient to induce these alterations. However, despite hormonal changes, OVX mice fed a FRD do not develop significant cardiac dysfunction.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 7","pages":"1114-1133"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Deciphering the signaling landscape of YAP in the tumor microenvironment—Insights into hepatocellular carcinoma progression 解读肿瘤微环境中YAP的信号传导格局——对肝细胞癌进展的洞察。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-02-24 DOI: 10.1002/1873-3468.70310

Prachi Sharma, Shaikh Maryam Ghufran, Bornika Roy, Sampa Ghose, Subhrajit Biswas

{"title":"Deciphering the signaling landscape of YAP in the tumor microenvironment—Insights into hepatocellular carcinoma progression","authors":"Prachi Sharma, Shaikh Maryam Ghufran, Bornika Roy, Sampa Ghose, Subhrajit Biswas","doi":"10.1002/1873-3468.70310","DOIUrl":"10.1002/1873-3468.70310","url":null,"abstract":"<p>Liver cancer stands as the sixth leading cause of cancer-related deaths globally, with hepatocellular carcinoma (HCC) being the most frequently diagnosed subtype. The hepatic tumor microenvironment (TME) comprises a complex array of cellular and non-cellular components, including activated hepatic stellate cells (HSCs), tumor-associated macrophages (TAM), endothelial cells, immune cells, and non-cellular elements such as growth factors, proteolytic enzymes, inhibitors, and extracellular matrix (ECM) proteins. The initiation and progression of HCC involve intricate interactions among hepatocytes, tumor cells, and non-tumor cells, including liver-resident non-parenchymal cells (NPCs). The Hippo-YAP pathway plays a crucial role in tumor development and initiation. YAP/TAZ, as primary effectors of the Hippo pathway, intricately connect with other signaling pathways relevant to tumors. YAP promotes the growth of cancer stem cells, the development of malignant phenotypes, and drug resistance, contributing significantly to cancer growth. This review focuses on the role of YAP in stromal cells as a mediator of HCC. We aim to present a comprehensive overview, not only consolidating existing knowledge but also paving the way for innovative exploration in pursuing effective therapeutic strategies against HCC.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"600 7","pages":"1006-1027"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Ischemic heart disease-associated ∆M1-Q91 PDE5A2 mutant shows reduced efficacy for cGMP, but not sildenafil, binding-induced conformational change 缺血性心脏病相关的∆M1-Q91 PDE5A2突变体对cGMP的疗效降低，但对西地那非结合诱导的构象改变没有影响。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-13 Epub Date: 2026-02-02 DOI: 10.1002/1873-3468.70292

Wesam S. Ahmed, Asma Fatima, Anupriya M. Geethakumari, Kabir H. Biswas

引用次数: 0

Plasmodium falciparum ring-infected erythrocyte surface antigen 3 (PfRESA3) is a cytoskeleton-interacting protein and potential co-chaperone. 恶性疟原虫环感染红细胞表面抗原3 （PfRESA3）是一种细胞骨架相互作用蛋白和潜在的共伴侣蛋白。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-12 DOI: 10.1002/1873-3468.70340

Nipa Rani Mallick, Welka Sahu, Deepak Kumar Ojha, Shivashis Mund, Aleena Das, Ankit Kumar Pati, Selvakumar Elangovan, K Sony Reddy

{"title":"Plasmodium falciparum ring-infected erythrocyte surface antigen 3 (PfRESA3) is a cytoskeleton-interacting protein and potential co-chaperone.","authors":"Nipa Rani Mallick, Welka Sahu, Deepak Kumar Ojha, Shivashis Mund, Aleena Das, Ankit Kumar Pati, Selvakumar Elangovan, K Sony Reddy","doi":"10.1002/1873-3468.70340","DOIUrl":"https://doi.org/10.1002/1873-3468.70340","url":null,"abstract":"<p><p>Plasmodium falciparum exports proteins into host erythrocytes for survival, but the roles of many of these proteins remain unexplored. Here, we used recombinant protein constructs and antibodies corresponding to Plasmodium falciparum ring-infected erythrocyte surface antigen-3 (PfRESA3) to identify it as a dense granule merozoite protein exported early to the inner erythrocyte membrane, where it associates with the cytoskeleton. Constructs lacking the J domain bound inside-out vesicles, implicating PRESAN and DnaJ-X in cytoskeletal interactions. Recombinant PfRESA3 constructs stimulated the ATPase activity of human HsHSPA8 and enhanced malate dehydrogenase (MDH) refolding. However, truncated PfRESA3 constructs did not significantly enhance MDH refolding by HsHSPA8. These findings suggest PfRESA3 modulates host HsHSPA8 to support cytoskeletal remodeling/parasite protein folding early in infection. Impact statement Our study uncovers a high-stakes hijacking of the human erythrocyte by Plasmodium falciparum. By identifying PfRESA3 as a potential co-chaperone that anchors to the host's cytoskeleton and recruits human chaperones, this study reveals a sophisticated survival strategy. It exposes a critical vulnerability in the parasite's early development inside the human erythrocyte.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

TNFR2 signaling promotes monocytic-MDSC differentiation and production of immunosuppressive mediators. TNFR2信号传导促进单核细胞- mdsc分化和免疫抑制介质的产生。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-01 Epub Date: 2026-02-24 DOI: 10.1002/1873-3468.70314

Yuta Tsuji, Masaki Inoue, Tomoya Okuda, Momona Murata, Shogo Imagaki, Nanami Taniyama, Honoka Yoshikawa, Hanae Kuroiwa, Shin-Ichi Tsunoda

引用次数: 0

STING agonists as antiviral agents. 作为抗病毒药物的STING激动剂。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-01 Epub Date: 2025-12-17 DOI: 10.1002/1873-3468.70251

Tiffany S Nelson, Zhe Ma

引用次数: 0

Mechanisms of IgE-mediated food allergy and the role of allergen-specific B cells. ige介导的食物过敏机制及过敏原特异性B细胞的作用。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-01 Epub Date: 2026-02-19 DOI: 10.1002/1873-3468.70305

Juan-Felipe López, Özge Yilmaz Ardicli, Mübeccel Akdis

{"title":"Mechanisms of IgE-mediated food allergy and the role of allergen-specific B cells.","authors":"Juan-Felipe López, Özge Yilmaz Ardicli, Mübeccel Akdis","doi":"10.1002/1873-3468.70305","DOIUrl":"10.1002/1873-3468.70305","url":null,"abstract":"<p><p>The substantial increase in food allergy prevalence during the last decades has made it a significant public health concern, affecting around 10% of the global population, especially children. Despite significant progress in understanding the general mechanisms of allergic sensitization, the development of oral tolerance remains a major challenge in advancing food allergy research and treatment. Additionally, each allergenic food source has a distinct immunological profile and tolerance trajectory, further complicating research efforts. Currently, oral allergen-specific immunotherapy is the only treatment that can help build tolerance to certain food allergens over time-although treatment outcomes vary. While B cells have been described and studied for their pathogenic role in food allergy, recent evidence suggests that they also modulate allergic responses through various effector and humoral functions. Notably, despite their low frequency, recent knowledge on the molecular and functional characteristics of food allergen-specific memory B cells has revealed important functions during both disease progression and therapeutic intervention. This review summarizes the current knowledge of IgE-mediated food allergy, highlighting the role of B cells, especially allergen-specific ones, in both disease and immune tolerance.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":"1137-1150"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

GDNF-RET signaling drives pulmonary neuroendocrine cell hyperplasia and allergic airway inflammation. GDNF-RET信号驱动肺神经内分泌细胞增生和过敏性气道炎症。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-01 Epub Date: 2026-04-12 DOI: 10.1002/1873-3468.70341

Tasuku Kawano, Erina Ike, Suguru Okada, Tomoko Takahashi

{"title":"GDNF-RET signaling drives pulmonary neuroendocrine cell hyperplasia and allergic airway inflammation.","authors":"Tasuku Kawano, Erina Ike, Suguru Okada, Tomoko Takahashi","doi":"10.1002/1873-3468.70341","DOIUrl":"10.1002/1873-3468.70341","url":null,"abstract":"<p><p>Pulmonary neuroendocrine cell (PNEC) hyperplasia often occurs in lung diseases, including allergic asthma. We previously reported that PNEC-derived calcitonin gene-related peptide (CGRP) likely stimulates group 2 innate lymphoid cells (ILC2), exacerbating asthma phenotypes in a mouse model. Here, we investigate the role of glial cell-line derived neurotrophic factor (GDNF) and rearranged during transfection (RET) signaling in PNEC hyperplasia and its therapeutic potential in asthma. PNECs expressed GDNF receptors, which were activated primarily by infiltrating inflammatory cells. Application of a RET-specific inhibitor suppressed ILC2 levels, PNEC hyperplasia and airway allergic responses. We suggest that GDNF-RET signaling promotes PNEC hyperplasia and that the PNEC-CGRP-ILC2 axis is closely associated with the development of allergic asthma, presenting a possible new treatment strategy. Impact statement Our study is the first to indicate the possibility of controlling pulmonary neuroendocrine cell (PNEC) hyperplasia and acute allergic airway inflammation through RET signaling, which could lead to elucidating the mechanism underlying the PNEC hyperplasia-immune relationship in asthma. We propose that targeting this could be a new treatment strategy.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":"1185-1198"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Multiple ETS family transcription factors bind mutant p53 via distinct interaction regions. 多个ETS家族转录因子通过不同的相互作用区域结合突变p53。

IF 3 4区生物学

FEBS Letters Pub Date : 2026-04-01 Epub Date: 2025-12-31 DOI: 10.1002/1873-3468.70260

Stephanie A Metcalf, Nicholas F Downing, Kaitlyn M Mills, Samuel C Metcalfe, Alexander E Kritzer, Lindsey D Mayo, Peter C Hollenhorst

{"title":"Multiple ETS family transcription factors bind mutant p53 via distinct interaction regions.","authors":"Stephanie A Metcalf, Nicholas F Downing, Kaitlyn M Mills, Samuel C Metcalfe, Alexander E Kritzer, Lindsey D Mayo, Peter C Hollenhorst","doi":"10.1002/1873-3468.70260","DOIUrl":"10.1002/1873-3468.70260","url":null,"abstract":"<p><p>ETS family transcription factors can mediate mutant p53 functions, but there has been no comprehensive analysis of p53 interaction across the ETS family. By comparing direct mutant p53 binding between 26 ETS proteins, we found that all bound mutant p53, but relative binding differed significantly. The ETS DNA binding domain provided a common interaction interface, but strong binding required an alternate interaction domain highlighted by a PXXPP motif found in five ETS proteins. Genome-wide mapping found that the ETS protein ERG mediated some mutant p53 DNA binding in prostate cancer cells. Lastly, ETS proteins that interact strongly with mutant p53 tended to be upregulated in p53 mutant ovarian cancer. These results identify multiple ETS family members that could mediate mutant p53 function in cancer. Impact statement The mechanisms behind gain-of-function mutant p53 remain unclear. Here we identify distinct domains and a novel motif that can mediate binding of mutant p53 to multiple different ETS family transcription factors.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":"1248-1262"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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