Cellular and Molecular Life Sciences最新文献

{"title":"USP1 inhibits influenza A and B virus replication in MDCK cells by mediating RIG-I deubiquitination.","authors":"Yuejiao Liao, Siya Wang, Tian Tang, Chengfan Li, Chenhao Yang, Liyuan Ma, Jin Ye, Jiamin Wang, Di Yang, Zilin Qiao, Zhongren Ma, Zhenbin Liu","doi":"10.1007/s00018-025-05733-6","DOIUrl":"https://doi.org/10.1007/s00018-025-05733-6","url":null,"abstract":"<p><p>The post-translational modification and stability regulation of RIG-I play critical roles in promoting IFN-I production and maintaining immune homeostasis. In this study, we found that ubiquitin-specific peptidase 1 (USP1) promotes RIG-I protein stability through deubiquitination, which in turn enhances antiviral immunity through the production of inflammatory cytokines, and inhibits the replication of influenza virus in MDCK cells. In contrast, USP1 knockdown inhibited the deubiquitination of RIG-I, decreased the RIG-I protein level, and significantly increased the influenza virus titer. Meanwhile, inhibition of USP1 expression did not have a significant effect on the proliferation of MDCK cells, suggesting that USP1 could be used as a target gene to establish a vaccine-producing MDCK cell line. The above results provide a more comprehensive understanding of the function of USP1 and the antiviral response mechanism, and provide a theoretical and methodological basis for the screening of target genes for the artificial establishment of high-yield MDCK cell lines for vaccine production.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"200"},"PeriodicalIF":6.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging and chronic inflammation: impacts on olfactory dysfunction-a comprehensive review.","authors":"Yingqi Xie, Shenglei Wang, Xudong Cha, Fengzhen Li, Zengyi Xu, Jian Wu, Huanhai Liu, Wenwen Ren","doi":"10.1007/s00018-025-05637-5","DOIUrl":"10.1007/s00018-025-05637-5","url":null,"abstract":"<p><p>Olfactory dysfunction (OD) is a common nasal disease, particularly prevalent among the elderly population, significantly impacting the affected individuals' quality of life. This review focuses on the influence of aging and chronic inflammation on olfactory dysfunction, presenting insights from both the peripheral and central olfactory systems. By exploring the molecular mechanisms and pathological changes underlying the occurrence of olfactory dysfunction in relation to age-related diseases and chronic inflammation conditions, we aim to provide a comprehensive theoretical foundation for further research and offer valuable insights for more effective treatment of olfactory dysfunction.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"199"},"PeriodicalIF":6.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding microRNA arm switching: a key to evolutionary innovation and gene regulation.","authors":"Danillo Pinhal, Leandro de B Gonçalves, Vinícius F Campos, James G Patton","doi":"10.1007/s00018-025-05663-3","DOIUrl":"https://doi.org/10.1007/s00018-025-05663-3","url":null,"abstract":"<p><p>miRNA arm switching is a pivotal regulatory mechanism that allows organisms to fine-tune gene expression by selectively utilizing either the 5p or 3p strand of a miRNA duplex. This process, conserved across species, facilitates adaptive responses to developmental cues, environmental changes, and disease states. By dynamically altering strand selection, arm switching reshapes gene regulatory networks, contributing to phenotypic diversity and evolutionary innovation. Despite its growing recognition, the mechanisms driving arm switching-such as thermodynamic properties and enzyme-mediated processing-remain incompletely understood. This review synthesizes current findings, highlighting arm switching as a highly conserved mechanism with profound implications for the evolution of regulatory networks. We explore how this phenomenon expands miRNA functionality, drives phenotypic plasticity, and co-evolves with miRNA gene duplications to fuel the diversification of biological functions across taxa.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"197"},"PeriodicalIF":6.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of intraflagellar transport protein IFT140 in the formation and function of motile cilia in mammals.","authors":"Yi Tian Yap, Jiehong Pan, Jian Xu, Shuo Yuan, Changmin Niu, Cheng Zheng, Wei Li, Ting Zhou, Tao Li, Yong Zhang, Michael J Holtzman, Gregory J Pazour, Rex A Hess, Christopher V Kelly, Aminata Touré, Steven L Brody, Zhibing Zhang","doi":"10.1007/s00018-025-05710-z","DOIUrl":"https://doi.org/10.1007/s00018-025-05710-z","url":null,"abstract":"<p><p>Cilia are microtubular structures extending from the surface of most mammalian cells. They can be categorized as motile cilia and primary sensory cilia. Both types possess intraflagellar transport (IFT) machinery, composed of unique protein complexes that travel along the microtubules to deliver proteins for ciliary and flagellar assembly, disassembly, and homeostasis. Although the role of IFT in primary cilia formation has been well studied, little is known about its role in mammalian motile cilia assembly. We generated conditional knockout mice by breeding floxed Ift140 mice with the FOXJ1-Cre transgenic mouse line to specifically delete Ift140 from cells that assemble motile cilia. Mice with Ift140 deficiency did not have laterality defects or gross; however most died prior to sexual maturity. Those mutants that survived to adulthood were completely infertile. Males demonstrated abnormal spermatogenesis associated with reduced sperm count and motility, together with short length flagella, and abnormal morphology. Cilia length was diminished in the epithelial cells of the efferent ductules and airways. Cilia from cultured tracheal epithelial cells were also short and had reduced beat frequency (CBF). Ultrastructural studies revealed the presence of inner and outer dynein arms, but an abnormal central apparatus, and the accumulation of particles within the cilia. Overall, the short length and abnormal localization of ciliary proteins in Ift140 conditional mutants resulted in inadequate cilia function despite proper localization of the dynein motor complexes. We propose a key role of Ift140 for motile cilia assembly in certain tissues and suggest that genetic alterations of IFT140 could be associated with motile ciliopathies.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"198"},"PeriodicalIF":6.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human-specific genomic evolution of a regulatory network enables fine-tuning of N-cadherin gene expression.","authors":"Éva Erdmann, Savera Agolli, Simon Fix, Félicie Cottard, Christine Keyser, Vincent Zvenigorosky, Angéla Gonzalez, Zakary Haili, Bruno Kieffer, Jocelyn Céraline","doi":"10.1007/s00018-025-05725-6","DOIUrl":"https://doi.org/10.1007/s00018-025-05725-6","url":null,"abstract":"<p><p>Androgen receptor (AR), a member of the nuclear receptor superfamily controls prostate epithelial cell plasticity by repressing a panel of genes involved in epithelial-mesenchymal transition (EMT), including the human CDH2 gene encoding N-cadherin. At the opposite, pathological AR variants such as AR-V7 associated with prostate tumor progression upregulate those EMT genes. Here, focusing on the human CDH2 gene, we show that this duality between AR and AR-V7 relies on a potential human accelerated region present in the intron 1. This fastest-evolving region of the human genome is actually a variable number tandem repeat (VNTR) comprising 24 repetitions of a DNA sequence that englobes binding sites for steroid hormone receptors, recombination signal binding protein for immunoglobulin kappa j region (RBPJ) an effector of the Notch pathway, and zinc finger e-box binding homeobox 1 (ZEB1). Genomic DNA sequencing, multiple sequence alignment, data mining, as well as protein-DNA interaction and gene expression analyses indicate that this VNTR constitutes a potential transcriptional hub for different transcription factors to control human CDH2 expression. Also, our data suggest that prostate tumor cells may unlock an up to now unknown molecular mechanism associated with a fine-tuned control of human CDH2 gene expression.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"196"},"PeriodicalIF":6.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of cortical microtubule organization in epidermal keratinocytes.","authors":"Keying Guo, Andreas Merdes","doi":"10.1007/s00018-025-05714-9","DOIUrl":"https://doi.org/10.1007/s00018-025-05714-9","url":null,"abstract":"<p><p>Microtubules in many differentiated cell types are reorganized from a radial, centrosome-bound array into a cell type-specific, non-centrosomal network. In epidermal keratinocytes, a subset of microtubules is organized from the cell cortex. These microtubules are anchored to desmosomes, with ninein serving as a linker protein. Details of this organization are poorly understood. We used immunofluorescence expansion microscopy to visualize directly the contact between cortical microtubules and desmosomes in murine skin tissue. Microtubule bound laterally to desmosomes, or with their ends at mixed polarity. Experiments including time-lapse microscopy of EB3-GFP, microtubule regrowth after depolymerization, and expression of ectopic ninein that was sequestered to the plasma membrane by a CAAX sequence motif, indicated that nucleation of microtubules doesn't occur at the cortex. Experimental severing of microtubules by spastin led to accumulation of microtubules next to ectopic, cortical ninein. Overall, our data suggest that microtubules accumulate by translocation from non-cortical sites towards sites of cortical ninein.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"193"},"PeriodicalIF":6.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct regulation of Per2 by Roraa: insights into circadian and metabolic interplay in zebrafish.","authors":"Miao Yang, Yan Liu, Zhilin Zhong, Yue Ou, Mingyong Wang, Yingbin Zhong, Chao Liu","doi":"10.1007/s00018-025-05696-8","DOIUrl":"https://doi.org/10.1007/s00018-025-05696-8","url":null,"abstract":"<p><p>Circadian rhythms are fundamental for regulating physiological processes in organisms, with disruptions often linked to metabolic disorders. This study investigated the role of the roraa gene in zebrafish, particularly its influence on circadian rhythms and metabolic regulation. Using quantitative PCR and in situ hybridization, we confirmed the rhythmic expression of roraa and explored its oscillatory mechanisms. The construction of roraa knockout mutants revealed that the absence of roraa disrupts circadian clock function, as evidenced by the reduced expression of core clock genes and altered behavioral rhythms, while the transgenic zebrafish lines which overexpress roraa just have opposite results. Additionally, we demonstrated that Roraa directly regulates per2 expression through the RORE element in its promoter. Furthermore, the transcriptome analysis and quantitative PCR indicated that the metabolism related genes, especially lipid metabolism related genes were obviously changed in roraa-/- mutants compare with WT. Our findings underscore the critical role of Roraa in coordinating circadian and metabolic processes, providing insights into potential therapeutic targets for addressing metabolic disorders related to circadian disruption.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"195"},"PeriodicalIF":6.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clofoctol impairs the stemness of gastric cancer and induces TNF-mediated necroptosis by directly binding to RanBP2.","authors":"Yi Liu, Yanhui Ma, Bingqian Zhou, Bingxian Bian, Yunlan Zhou, Shiyu Chen, Peng Zhang, Lisong Shen, Hui Chen","doi":"10.1007/s00018-025-05723-8","DOIUrl":"https://doi.org/10.1007/s00018-025-05723-8","url":null,"abstract":"<p><p>Gastric cancer stem cells (GCSCs) play a crucial role in the initiation, progression, recurrence and therapeutic resistance, contributing to a poor prognosis. Consequently, GCSCs are deemed to be a potential therapeutic target for gastric cancer (GC). Although β-catenin is a well-recognized therapeutic target for GC and several inhibitors have demonstrated potent anti-tumor effects, there is a dearth of therapeutic agents targeting β-catenin for clinical therapy. In this study, we carried out high-throughput screening of clinically approved drugs to identify effective inhibitors of β-catenin. The results revealed that the antibiotic drug, clofoctol (CFT) effectively reduced the β-catenin level, attenuated stemness traits both in vitro and in vivo, and induced necroptosis of GCSCs. Further analyzing of downstream genes and targeted proteins, we found that CFT inhibited GCSCs viability by binding to the SUMO E3 ligase RanBP2, thereby suppressing the SerpinE1/β-catenin axis and activating TNF-mediated necroptosis. These results indicate that CFT may exert potent therapeutic effects against GC by targeting β-catenin and inhibiting the viability of GCSCs.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"194"},"PeriodicalIF":6.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibulin-1 deficiency alleviates liver fibrosis by inhibiting hepatic stellate cell activation via the p38 MAPK pathway.","authors":"Wenshan Zhao, Jingyu Zhang, Qingdong Guo, Qi Wang, Hong Zhao, Fan Xiao, Ming Han, Ying Cao, Rui Ding, Aiting Yang, Wen Xie","doi":"10.1007/s00018-025-05647-3","DOIUrl":"https://doi.org/10.1007/s00018-025-05647-3","url":null,"abstract":"<p><p>Elastin stabilization has been correlated with the reversibility of fibrosis. Fibulin-1 can participate in elastin assembly, which promotes its stabilization. However, the role of Fibulin-1 in liver fibrosis remains unknown. Here, we performed a proteomics analysis to identify notable changes in Fibulin-1 expression during continuous fibrosis progression and regression. Fibulin-1 expression was dramatically increased in the plasma of patients with cirrhosis as well as in liver fibrosis models and hepatic stellate cells (HSCs) treated with TGF-β1, and significant accumulation of Fibulin-1 was observed in chronic hepatitis B (CHB)- and metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis. Functional studies demonstrated that Fibulin-1 silencing inhibited HSC activation, while the opposite effects were observed for Fibulin-1 overexpression in vitro. Furthermore, transcriptomic analysis revealed that Fibulin-1 mediated p38 MAPK pathway activation, which was confirmed by the addition of a p38 MAPK inhibitor. More importantly, Fibulin-1 depletion in a CCl₄-induced liver fibrosis model substantially ameliorated fibrosis progression, which was accompanied by decreased profibrogenic gene expression and decreased levels of insoluble elastin. Moreover, activation of the p38 MAPK pathway was inhibited in vivo. The expression of Fibulin-1D, rather than Fibulin-1C, was elevated during liver fibrogenesis, which suggested a major role for Fibulin-1D in liver fibrosis. Next, we established Fibulin-1D/elastin-coated culture models with LX-2 cells. LX-2 cells with extracellular elastin and Fibulin-1D deposition showed more significant profibrotic phenotypic alterations than those with elastin alone. Fibulin-1 deficiency alleviated liver fibrosis by reducing insoluble elastin and HSC activation, and finally, the p38 MAPK pathway might be involved in the effect of Fibulin-1 on HSCs.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"192"},"PeriodicalIF":6.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β2-tubulin regulates the development and migration of eupyrene sperm in Spodoptera frugiperda.","authors":"Hao Sun, Ling-Ao Bu, Xin-Yue Zhang, Zhi-Ruo Zhang, Shao-Cong Su, Di Guo, Cong-Fen Gao, Subba Reddy Palli, Jackson Champer, Shun-Fan Wu","doi":"10.1007/s00018-025-05722-9","DOIUrl":"https://doi.org/10.1007/s00018-025-05722-9","url":null,"abstract":"<p><p>Spermatogenesis is the basis of sexual reproduction and is essential for the propagation of insect populations. Understanding the process of spermatogenesis and identifying key genes involved in sperm function can aid in developing pest genetic control methods. The testis-specific gene β2-tubulin (B2t) is crucial for spermatogenesis in insects possessing monomorphic spermatids. However, the role of B2t in lepidopteran dimorphic spermatogenesis remains unclear. In this study, we explored the effect of B2t in the development of eupyrene and apyrene sperm in the Spodoptera frugiperda, a major global pest. Knockout of B2t resulted in male sterility. B2t mutations lead to abnormal development of eupyrene sperm and the inability of eupyrene sperm to transfer from the testis to the double ejaculatory ducts. However, disruption of B2t did not affect apyrene spermatogenesis and migration. Interestingly, we found that first mating with B2t-null males inhibited sperm fertilization from a second wild-type male. Cage studies and mathematical modeling analyses suggested that releasing excessive B2t-null males suppressed female fertility. Our study provides insights into dimorphic spermatogenesis in lepidopteran pests and an efficient molecular target for pest genetic control techniques.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"191"},"PeriodicalIF":6.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}