FEBS Open Bio最新文献

{"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, Di Liu, Bing Liu, Yu Lan, Jie Zhou","doi":"10.1002/2211-5463.70078","DOIUrl":"https://doi.org/10.1002/2211-5463.70078","url":null,"abstract":"<p><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":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Kanari Taki, Asuka Hayami, Komachi Kato, Yuka Nozaki, Yuhei Mizunoe, Takumi Narita, Ryoichi Mori, Yoshikazu Higami, Masaki Kobayashi","doi":"10.1002/2211-5463.70077","DOIUrl":"https://doi.org/10.1002/2211-5463.70077","url":null,"abstract":"<p><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 Pgc-1α and Mipep. 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 Pgc-1α single-OE cells and double-OE cells. Notably, double-OE cells exhibited increased mRNA levels of phosphoethanolamine/phosphocholine phosphatase 1 (Phospho1), which plays a role in phospholipid metabolism and non-canonical thermogenesis. Phospho1 expression was also increased in white adipose tissue of mice under caloric restriction. In summary, the double OE of Pgc-1α and Mipep induced Phospho1 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":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Evgenia Tsoukala, Theodora D Sarantopoulou, Maria-Elpida Christopoulou","doi":"10.1002/2211-5463.70074","DOIUrl":"10.1002/2211-5463.70074","url":null,"abstract":"<p><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":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current trends in single-cell RNA sequencing applications in diabetes mellitus.","authors":"Seyed Sajjad Zadian, Khodakaram Jahanbin, Shekoofeh Nikooei, Marzieh Rostaminejad, Arezoo Rahimi, Pedram Abdizadeh, Behnam Alipoor","doi":"10.1002/2211-5463.70061","DOIUrl":"10.1002/2211-5463.70061","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is among the most prevalent metabolic diseases worldwide, associated with an increased risk of mortality. Although numerous studies have been conducted to uncover the cellular and molecular pathways associated with DM pathogenesis, reaching new diagnosis and treatment goals for DM requires further research. The progress in gene sequencing technologies, particularly in single-cell RNA sequencing (scRNA-seq), has yielded additional insights into the molecular pathways involved in the development and progression of DM. This review summarizes the latest advances and applications of RNA-seq technologies in diabetes research, such as the characterization of single human islet and immune cells in DM, and the applications of scRNA-seq in the treatment and early diagnosis of diabetes complications.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332717","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":"Interaction of class III cellobiose dehydrogenase with lytic polysaccharide monooxygenase.","authors":"Angela Giorgianni, Florian Csarman, Peicheng Sun, Mirjam Kabel, Roland Ludwig","doi":"10.1002/2211-5463.70067","DOIUrl":"https://doi.org/10.1002/2211-5463.70067","url":null,"abstract":"<p><p>The genome of Fusarium solani, a well-known plant pathogen, encodes various lytic polysaccharide monooxygenases (LPMOs) involved in plant biomass degradation in combination with cellobiose dehydrogenase (CDH). To investigate the auxiliary role of the recently expressed and characterized class III CDH from F. solani (FsCDH), this enzyme was tested in combination with the well-characterized AA9C from Neurospora crassa (NcAA9C). Steady-state and stopped-flow methods as well as electrochemical measurements demonstrate how FsCDH efficiently transfers electrons to NcAA9C, with a rapid, observed heme reoxidation rate constant of 129 s^-1. In comparison to ascomycete class II CDHs, the H₂O₂ production by FsCDH is insufficient to promote LPMO activity. However, a cyclic cascade between NcAA9C and FsCDH was found. NcAA9C reaction products showed a high catalytic efficiency as FsCDH substrates, with K_M values close to its natural substrate cellobiose. This reaction was further investigated by a real time measurement, where FsCDH and NcAA9C were incubated with phosphoric acid-swollen cellulose and the reaction was sustained over a long period without the addition of an external reductant. The new class III CDH is similar to other CDH classes, except its very low reactivity with molecular oxygen, pointing towards a different function in Ascomycota than class II CDH. These findings contribute to the better understanding of oxidative cellulose degradation by fungi and thus, to potential biotechnological applications for the sustainable use of biomass.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316261","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":"Gut alterations in a chronic kidney disease rat model with diet-induced vascular calcification.","authors":"Piotr Bartochowski, Irene Cortijo, Shruti Bhargava, Bernard Jover, Fabrice Raynaud, Juliana H Boukhaled, Anne-Dominique Lajoix, Vera Jankowski, Joachim Jankowski, Magali Cordaillat-Simmons, Àngel Argilés, Nathalie Gayrard, Flore Duranton, Jonas Laget","doi":"10.1002/2211-5463.70043","DOIUrl":"https://doi.org/10.1002/2211-5463.70043","url":null,"abstract":"<p><p>Intestinal disorders and vascular calcification (VC) are often associated with chronic kidney disease (CKD). While gut barrier alterations have been reported in CKD (such as abnormal intestinal permeability, bacterial overgrowth, and inflammation), it is not clear if vascular calcification influences these alterations. To investigate whether the bidirectional relationships between VC and gut dysfunction could be mediated by increased inflammation and uremic toxin generation, we used the SNx-VC model of uremic vascular calcification (rats undergoing subtotal 5/6th nephrectomy and fed a procalcifying high-phosphate and vitamin D diet). We confirmed the presence of CKD and VC by von Kossa staining and observed increased gut-origin uremic toxin, indoxyl sulfate (IS), in SNx-VC animals compared to controls. In SNx-VC rats, we observed decreased mucus production (Alcian blue, Mucin 2 staining) in the colon and ileum which was correlated with the level of calcification. There was no change in inflammation markers or tight junction protein expression. We assessed intestinal levels in the NOD-like receptor family pyrin domain containing 6 (NLRP6) protein, known to regulate mucus secretion, and found no change in the colon or ileum. Nlrp6 mRNA was, however, decreased in the colon of SNx-VC rats, along with other mRNA (Ly96, Sod1), while Tlr2 was increased compared to controls. Our observations of low mucus, low Nlrp6 mRNA, and high IS in SNx-VC rats confirm a link between gut barrier alterations and uremic VC. This suggests that alterations in the mucus layer could favor the generation of gut-origin uremic toxins and promote VC in CKD. Thus, improving the gut mucus barrier function in the context of uremic VC could be considered as a possible therapeutic strategy in CKD patients.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316260","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":"Genetic diversity and population structure of the Taigan dog breed.","authors":"Kira Bespalova, Anastassiya Perfilyeva, Мamura Begmanova, Assel Zhaxylykova, Arailym Yerzhan, Kanagat Yergali, Almazbek Akunov, Marat Munarbek Uulu, Anna Khamchukova, Almira Amirgaliyeva, Yelena Kuzovleva","doi":"10.1002/2211-5463.70065","DOIUrl":"https://doi.org/10.1002/2211-5463.70065","url":null,"abstract":"<p><p>The Taigan is an ancient sighthound breed native to the Tien Shan Mountains in Kyrgyzstan and adapted to hunting at high altitudes and in rough terrain. Previous studies have provided insights into its phylogenetic relationships, but more data are needed to determine whether the Taigan is genetically distinct from related sighthounds. In the present study, we conducted a comprehensive genetic analysis using short tandem repeat markers and high-density single nucleotide polymorphism array data to assess genetic diversity, population structure and differentiation from other sighthound breeds. The analysis showed high polymorphism and an excess of heterozygosity (F = -0.013), indicating a balanced genetic structure. Bayesian clustering identified five genetic clusters among the Taigans, with no dominant lineage, suggesting a diverse gene pool. Principal component analysis and admixture analyses assigned the Taigan to the eastern sighthound group, closely clustered with the Kazakh Tazy. A pairwise F_ST analysis showed only 17 highly divergent single nucleotide polymorphisms. This number is significantly lower than in recognized and well-differentiated breed pairs and suggests that genetic differentiation between Kazakh Tazy and Taigan breeds is minimal under current sampling conditions. Further studies with larger data sets are needed to determine the genetic divergence between the Taigan and the Kazakh Tazy.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316259","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}