FEBS Open Bio最新文献

{"title":"Actin dynamics controlled by IqgC, a RasGAP at the crossroads between the IQGAP and fungal GAP1 families.","authors":"Vedrana Filić, Darija Putar, Lucija Mijanović, Igor Weber","doi":"10.1002/2211-5463.70083","DOIUrl":"https://doi.org/10.1002/2211-5463.70083","url":null,"abstract":"<p><p>In addition to transmitting receptor-mediated signals to adjust the gene expression profile of the cell, small GTPases of the Ras family also control the remodelling of the actin cytoskeleton. The conversion of Ras GTPases from their active to their inactive form is controlled by Ras GTPase-activating proteins (RasGAPs). IqgC, a RasGAP from Dictyostelium discoideum, was originally assigned to the IQGAP family, but its sequence and recent functional analyses show that IqgC is more closely related to RasGAPs from the GAP1 family of fungi. IqgC has two prominent domains, a RasGAP domain and a C-terminal RGCt domain, and interacts with Ras, Rab and Rap GTPases, but shows GTPase-promoting activity only towards Ras. IqgC suppresses macroendocytosis but supports cell-substratum adhesion and directed cell migration. Its localisation to macroendocytic cups is mediated by the RasGAP domain, whereas its localisation in ventral focal adhesions is mediated by the RGCt domain. We hypothesise that IqgC plays an important role in the balance between the competing feeding and migratory behaviour of amoeboid D. discoideum cells.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607882","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}

{"title":"Microfluidic electro-viscoelastic manipulation of extracellular vesicles.","authors":"Seyedamirhosein Abdorahimzadeh, Éva Bozó, Zikrullah Bölükkaya, Artem Zhyvolozhnyi, Anatoliy Samoylenko, Henrikki Liimatainen, Seppo J Vainio, Caglar Elbuken","doi":"10.1002/2211-5463.70080","DOIUrl":"https://doi.org/10.1002/2211-5463.70080","url":null,"abstract":"<p><p>Microfluidic technology has created new opportunities for developing innovative tools for biological applications. Given the significance of extracellular vesicles (EVs), extensive research has focused on developing microfluidic techniques for EV isolation. This research protocol presents electro-viscoelastic microfluidics as a novel approach for manipulating EVs. The system leverages the viscoelasticity of the suspending medium along with an externally applied electric field to alter EV motion within a microchannel. These findings suggest that our electro-viscoelastic microfluidic system has the potential for further development to be used for EV isolation.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599797","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}

{"title":"NMR screening of low molecular weight inhibitors targeting the papain-like protease (PLPro) of SARS-CoV-2","authors":"Dennis J. Pyper,&nbsp;Sridhar Sreeramulu,&nbsp;Benjamin T. Lanham,&nbsp;Elizabeth M. Engle,&nbsp;David Fushman,&nbsp;Harald Schwalbe","doi":"10.1002/2211-5463.70082","DOIUrl":"10.1002/2211-5463.70082","url":null,"abstract":"<p>The Papain-like protease (PLPro) from SARS-CoV-2 plays an important role in the cleavage of the polyproteins Pp1a and Pp1ab as well as in the suppression of the immune response by deISG15ylation. Considerable effort is therefore devoted to developing low molecular weight inhibitors as starting points for antiviral drugs. Here, we present the results of an NMR screening study of PLPro for binding to the DSI-poised fragment library containing 607 compounds. Based on saturation-transfer difference (STD)- and WaterLOGSY-NMR experiments, we identified 86 binding compounds. We prioritized five candidates for further in-depth analysis. For three of those, we determined dissociation constants and two distinct binding sites on PLPro. These compounds could serve as a basis for future drug design studies in medicinal chemistry.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 10","pages":"1667-1677"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539733","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}

{"title":"Liver-specific lncRNAs associated with liver cancers","authors":"Olga Y. Burenina,&nbsp;Roman K. Makarchenko,&nbsp;Maria P. Rubtsova,&nbsp;Olga A. Dontsova","doi":"10.1002/2211-5463.70079","DOIUrl":"10.1002/2211-5463.70079","url":null,"abstract":"<p>Long non-coding RNAs (lncRNAs) are transcripts with a length more than 200 nt, which do not encode proteins and act just as RNA molecules. In general, lncRNAs have much more distinct tissue specificity than proteins, as they usually realize more peculiar regulatory functions. Their expression levels are often altered in a response to stress conditions, metabolic changes, development of different diseases, and carcinogenesis. Cancer-associated lncRNAs are widely considered as perspective and useful biomarkers. Thus, development of clinical tests, which include tissue-specific and cancer-specific lncRNAs, might significantly contribute to cancer diagnostics and/or prognosis of the disease. A number of lncRNAs is known to be dysregulated in liver tumors and considered as probable biomarkers. However, most of them are rather universally well-known lncRNAs associated with various cancers. In the present review, we aimed to shed light on other lncRNAs with preferential expression in liver and/or liver tumors, for example, <i>LINC01554</i>, <i>LINC01093</i>, <i>LINC01348, LINC02428</i>, <i>FAM99B</i>, <i>etc</i>. We summarized recent discoveries unveiling their dysregulation in liver malignancies and related cellular mechanisms in which they are involved and considered their significance as probable liver cancer biomarkers.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 9","pages":"1383-1405"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539732","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}

{"title":"The E3 ubiquitin ligase, RNF219, suppresses CNOT6L expression to exhibit antiproliferative activity.","authors":"Shou Soeda, Melissa Montrose, Akinori Takahashi, Risa Ishida, Sandrine Burriel, Nao Ohmine, Tohru Natsume, Shungo Adachi, Minsoo Kim, Tadashi Yamamoto","doi":"10.1002/2211-5463.70081","DOIUrl":"https://doi.org/10.1002/2211-5463.70081","url":null,"abstract":"<p><p>Despite the increasing evidence of the role of CCR4-NOT complex in posttranscriptional gene regulation, relatively little is known about its mode of action. In a search for novel CCR4-NOT interacting partners, we carried out mass spectrometry analysis of immunoprecipitates with antibodies against four different CCR4-NOT subunits and identified RNF219, ring finger protein 219. A pull-down assay revealed that the C-terminal part of RNF219 directly binds to the CNOT1 DUF3819 domain and is associated with ubiquitin ligase activity. RNF219 knock-down in HEK293T cells resulted in elevated expression of CNOT6L, accompanied by increased cell proliferation. The apparent antiproliferative activity of RNF219 was inversely correlated with the level of CNOT6L. Furthermore, RNF219 ubiquitinated CNOT6L in vitro. Our data suggest that RNF219 suppress CNOT6L expression through proteasome-mediated protein degradation. Intriguingly, low expression of RNF219 was associated with poor prognosis of triple-negative breast cancer patients. However, further studies would be required to confirm whether the impact of RNF219 activity on cancer progression is mediated by the CCR4-NOT complex.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539734","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}

{"title":"Characterization of ribosome heterogeneity during endothelial to hematopoietic transition","authors":"Xitong Tian,&nbsp;Di Liu,&nbsp;Bing Liu,&nbsp;Yu Lan,&nbsp;Jie Zhou","doi":"10.1002/2211-5463.70078","DOIUrl":"10.1002/2211-5463.70078","url":null,"abstract":"<p>Emerging evidence has demonstrated that ribosomes are not homogeneous structures with non-specialized functions. There are now several reports of heterogeneity in the composition and functional specialization of ribosomes. Ribosome heterogeneity functions in regulating the translation of specific mRNAs, and thus plays important roles in embryonic development. However, the panorama of ribosome heterogeneity during embryonic hematopoiesis has not yet been portrayed. Here, by leveraging our single-cell transcriptomic data and a published proteomic dataset, we depict the landscape of ribosomal heterogeneity during endothelial-to-hematopoietic transition (EHT). By precisely distinguishing the different ribosomal components, we found their number and expression levels showed dynamic changes during EHT. We also report stage-specific signatures of ribosomal components. For example, RPL27 and RACK1 exhibited up-regulated expression both in dual-omics analysis and immunofluorescence experiments during EHT. Interestingly, further spatial structure analysis revealed that RACK1 localized at the bottom of 40S small ribosomal subunit, indicating its potential role in regulating ribosome function. Taken together, our study not only highlights the ribosome heterogeneity during EHT, but also provides new clues to explore how these heterogeneous machineries regulate mRNA translation.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 10","pages":"1658-1666"},"PeriodicalIF":2.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527032","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}

{"title":"Co-overexpression of the caloric restriction-induced mitochondrial factors PGC-1α and MIPEP upregulates Phospho1 expression in adipocytes","authors":"Mamiko Ishimatsu,&nbsp;Kanari Taki,&nbsp;Asuka Hayami,&nbsp;Komachi Kato,&nbsp;Yuka Nozaki,&nbsp;Yuhei Mizunoe,&nbsp;Takumi Narita,&nbsp;Ryoichi Mori,&nbsp;Yoshikazu Higami,&nbsp;Masaki Kobayashi","doi":"10.1002/2211-5463.70077","DOIUrl":"10.1002/2211-5463.70077","url":null,"abstract":"<p>Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a master transcriptional cofactor for mitochondrial biogenesis. Mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase, plays an important role in the maturation and activation of mitochondrial proteins. Caloric restriction has lifespan-extending effects that are reportedly exerted through induced expression of PGC-1α and MIPEP in white adipose tissue. To evaluate how upregulation of PGC-1α and MIPEP contributes to changes in the cellular characteristics of adipocytes, this study examined the mitochondrial function and differentiation of 3T3-L1 preadipocytes with single overexpression (OE) or double OE of <i>Pgc-1α</i> and <i>Mipep</i>. Compared with single-OE cells, double-OE cells exhibited no significant changes in oxygen consumption rate or mitochondrial morphology, but did show increased mitochondrial DNA levels. White adipocyte cell differentiation was suppressed in both <i>Pgc-1α</i> single-OE cells and double-OE cells. Notably, double-OE cells exhibited increased mRNA levels of phosphoethanolamine/phosphocholine phosphatase 1 (<i>Phospho1</i>), which plays a role in phospholipid metabolism and non-canonical thermogenesis. <i>Phospho1</i> expression was also increased in white adipose tissue of mice under caloric restriction. In summary, the double OE of <i>Pgc-1α</i> and <i>Mipep</i> induced <i>Phospho1</i> expression and suppressed adipocyte maturation, with little effect on mitochondrial function. This study provides new insights into the mitochondria-related mechanism of caloric restriction in adipocytes.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 10","pages":"1643-1657"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505268","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}

{"title":"Phenotypic plasticity in a novel set of EGFR tyrosine kinase inhibitor-adapted non-small cell lung cancer cell lines.","authors":"Tharsagini V Nanthaprakash, Campbell W Gourlay, Ina Oehme, Michelle D Garrett, Jindrich Cinatl, Mark N Wass, Martin Michaelis","doi":"10.1002/2211-5463.70076","DOIUrl":"https://doi.org/10.1002/2211-5463.70076","url":null,"abstract":"<p><p>Here, we introduce novel sublines of the EGFR-mutant non-small cell lung cancer (NSCLC) cell lines HCC827 and HCC4006 adapted to the EGFR kinase inhibitors gefitinib (HCC827^rGEFI^2μm, HCC4006^rGEFI^1μm), erlotinib (HCC827^rERLO^2μm, HCC4006^rERLO^1μm) and afatinib (HCC827^rAFA^50nm, HCC4006^rAFA^100nm). All sublines displayed resistance to gefitinib, erlotinib, afatinib and the third-generation EGFR kinase inhibitor osimertinib that overcomes T790M-mediated resistance. HCC4006^rERLO^1μm displayed a spindle-like morphology in agreement with previous findings that had detected epithelial-mesenchymal transition (EMT) in its precursor cell line HCC4006^rERLO^0.5μm. EMT had also been reported for the HCC4006^rGEFI^1μm precursor cell line HCC4006^rGEFI^0.5μm and for HCC4006^rAFA^100nm, but the morphologies of HCC4006^rGEFI^1μm or HCC4006^rAFA^100nm did not support this, suggesting plasticity in EMT regulation during the drug adaptation process and in established resistant cell lines. Accordingly, HCC4006^rERLO^1μm displayed resistance to MEK and AKT inhibitors in contrast to its precursor HCC4006^rERLO^0.5μm. We also detected metabolic plasticity, that is a temporary Warburg metabolism, in HCC4006 and HCC827^rGEFI^2μm. Response profiles to cytotoxic anticancer drugs, kinase inhibitors and HDAC inhibitors resulted in complex patterns that were specific for each individual subline, indicating individual resistance phenotypes. All resistant sublines remained sensitive or displayed collateral sensitivity to at least one of the investigated drugs. In conclusion, the comparison of EGFR kinase-resistant NSCLC sublines with their precursor cell lines that had been previously characterised at a lower resistance level and metabolic investigations indicated phenotypic plasticity during the resistance formation process and in established cell lines. This plasticity may contribute to the well-known variability in cell line phenotypes observed between different laboratories and in intra-laboratory experiments.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505269","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}

{"title":"Preparation and characterization of renal cell peptides from fetal rats for their antitumor activity.","authors":"Zhe Zhang, Yuan Cao, Jing Du, Ying Zhang, Junxia Wang, Ying Yuan, Lianqing Sun","doi":"10.1002/2211-5463.70075","DOIUrl":"https://doi.org/10.1002/2211-5463.70075","url":null,"abstract":"<p><p>Bioactive peptides with potent antitumor activity are attractive therapeutic agents. The present study aimed to prepare renal cell peptides (RCPs) from fetal rats to test their antitumor activities in vitro. Candidate peptides were characterized by capillary HPLC and MS and their bioactivity was predicted using PeptideRanker. The predicted top 10 bioactive peptides were synthesized and tested for their cytotoxicity against different types of tumor cells by cell counting kit-8 assays and their half maximal inhibitory concentration values were calculated. Protease-digested < 3 kDa protein products reduced the viability of Michigan Cancer Foundation (MCF)-7 cells in a dose-dependent manner. Functionally, many candidate peptides were predicted to have antitumor activity and the top ten peptides (RCPs 1-10) were synthesized. Interestingly, RCP1, 5 and 6 displayed preferable cytotoxicity against human cancer MCF-7, A549, HCT-116, Hela, HepG2 and SGC-7901 cells and their cytotoxicity was dose-dependent. RCPs prepared from fetal rats displayed potent cytotoxicity preferably against different types of cancer cells in vitro in a dose-dependent manner which may be valuable for the treatment of malignant tumors.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505270","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}

{"title":"Matrix: a complex amalgam of structures and functions in tumor microenvironment","authors":"Spyros S. Skandalis,&nbsp;Evgenia Tsoukala,&nbsp;Theodora D. Sarantopoulou,&nbsp;Maria-Elpida Christopoulou","doi":"10.1002/2211-5463.70074","DOIUrl":"10.1002/2211-5463.70074","url":null,"abstract":"<p>Cancer cells surrounded by a rich diversity of nonmalignant cell types are collectively embedded in the matrix, which is a dynamic, intricate three-dimensional mesh of biomolecules with both structural and functional properties. The matrix contains proteins, carbohydrates, and other glycoproteins that facilitate essential cellular communication and impact in various ways a broad spectrum of cellular functions, such as anchoring cells, guiding migration, and shaping signal gradients driving cell growth, apoptosis, survival, and differentiation. This review deals with the complexity of this amalgam of structures and functions and highlights the importance of the tumor microenvironment in the maintenance and evolution of tumors by describing certain bioactive macromolecules of the matrix, such as proteoglycans, hyaluronan, collagens, elastin, matricellular proteins as well as their cellular receptors like integrins and CD44.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 10","pages":"1552-1569"},"PeriodicalIF":2.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340069","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}