Cellular and Molecular Life Sciences最新文献_第4页

Transcription factors as essential regulators of myometrial smooth muscle cell function during pregnancy and labor. 转录因子是妊娠和分娩期间子宫肌平滑肌细胞功能的重要调节因子。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-21 DOI: 10.1007/s00018-026-06341-8

Sabrina Martini, Palak Gujral, Eduardo Orozco-Alonso, James Saliba, Volker Blank

{"title":"Transcription factors as essential regulators of myometrial smooth muscle cell function during pregnancy and labor.","authors":"Sabrina Martini, Palak Gujral, Eduardo Orozco-Alonso, James Saliba, Volker Blank","doi":"10.1007/s00018-026-06341-8","DOIUrl":"10.1007/s00018-026-06341-8","url":null,"abstract":"Parturition is a tightly regulated process coordinated by myometrial smooth muscle cells, which generate the uterine contraction required for birth. Preterm labor, defined as labor occurring before 37 weeks of gestation, remains a significant clinical challenge due to its association with adverse short and long-term risks on neonatal and maternal health. Earlier and recent studies provide strong evidence that transcription factors are performing crucial functions in uterine smooth muscle cells. In this review, we focus on the PR/ER, PPAR, NF-κB, AP-1, NFE2L2, and MAFF transcription factors and provide a comprehensive overview of their respective roles in myometrial smooth muscle cell function and the labor process. We also briefly discuss other transcriptional regulators that have been linked to uterine quiescence during pregnancy, to activation of the labor process or to both functions. Collectively, these transcription factors control various cellular processes, including inflammation, regulation of cytokine, chemokine and metalloproteinase expression, oxidative stress response, prostaglandin synthesis, calcium signaling, and contractility. Monitoring and targeting these transcription factors and associated pathways in the uterus are key for delaying or preventing preterm labor through the design of novel diagnostic and therapeutic tools to improve birth outcomes.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535384","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}

引用次数: 0

Reduced KLF4 expression in endothelial cells triggers pulmonary vascular abnormalities associated with experimental congenital diaphragmatic hernia. 内皮细胞中KLF4表达降低引发实验性先天性膈疝相关的肺血管异常。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-20 DOI: 10.1007/s00018-026-06319-6

Heleen M Kool, Petra E Bürgisser, Gabriela G Edel, Anne Boerema-de Munck, Marjon Buscop-van Kempen, Panagiotis Liakopoulos, Petros Kolovos, Wilfred F J van Ijcken, Robbert J Rottier

{"title":"Reduced KLF4 expression in endothelial cells triggers pulmonary vascular abnormalities associated with experimental congenital diaphragmatic hernia.","authors":"Heleen M Kool, Petra E Bürgisser, Gabriela G Edel, Anne Boerema-de Munck, Marjon Buscop-van Kempen, Panagiotis Liakopoulos, Petros Kolovos, Wilfred F J van Ijcken, Robbert J Rottier","doi":"10.1007/s00018-026-06319-6","DOIUrl":"10.1007/s00018-026-06319-6","url":null,"abstract":"Congenital diaphragmatic hernia (CDH) is a rare anomaly with an incidence of 1 in 3000 live births and characterized by defective closure of the diaphragm, lung hypoplasia, and pulmonary vascular remodeling. Although several genes associated with the occurrence of CDH, no clear genetic component has been identified. Previously, we showed that CDH patients have vascular abnormalities already early in development, and that perivascular cells are affected in CDH. In the current study, we focused on early abnormalities in the nitrofen-induced CDH mouse model. Transcriptome analysis of FACS-sorted perivascular and endothelial cell populations from lungs of control and experimental mouse CDH revealed a high similarity in GO terms of differentially expressed genes (DEGs) between these populations, suggesting a disturbed interaction between endothelial cells and pericytes. The disturbed interaction is the basis for the aberrant development of the pulmonary vasculature in CDH. Furthermore, the RNA sequence data revealed reduced expression of the Kruppel like factor 4 (Klf4) gene in endothelial cells of CDH, which was confirmed with protein expression analysis. Furthermore, we show that KLF4 is an important up stream regulator of genes associated with vascular development and confirm that members of the NOTCH signaling pathway are differentially expressed, indicating that NOTCH signaling is disturbed in CDH. Collectively, our data support the importance of KLF4 in pulmonary angiogenesis and contribute to our previous data that pulmonary vessels in CDH patients are already affected before birth, which in turn may impact therapeutic strategies to reduce pulmonary hypertension associated with CDH.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520017","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}

引用次数: 0

SOX10-mediated regulation of the MiR-106a/363 cluster drives RAF inhibitor resistance in BRAF-mutant melanoma. sox10介导的MiR-106a/363簇调控驱动braf突变黑色素瘤中RAF抑制剂的耐药性。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-18 DOI: 10.1007/s00018-026-06354-3

Ying Li, Yu-le Yong, Zhe Zhi, ZhenZhen Lu, Zongguan Huang, Lanlan Cui, Mo Zhang, Zihao Wu, Yiming Hu, Guanfei Zhang, Xiaofei Zhao, Shujun Han, Yan Zheng, Yongping Shao

{"title":"SOX10-mediated regulation of the MiR-106a/363 cluster drives RAF inhibitor resistance in BRAF-mutant melanoma.","authors":"Ying Li, Yu-le Yong, Zhe Zhi, ZhenZhen Lu, Zongguan Huang, Lanlan Cui, Mo Zhang, Zihao Wu, Yiming Hu, Guanfei Zhang, Xiaofei Zhao, Shujun Han, Yan Zheng, Yongping Shao","doi":"10.1007/s00018-026-06354-3","DOIUrl":"10.1007/s00018-026-06354-3","url":null,"abstract":"Adaptive resistance to MAPK inhibitors remains a major clinical obstacle in BRAF-mutant melanoma, driven by reversible transcriptional and epigenetic reprogramming. Previous studies have implicated loss of SRY-box transcription factor 10 (SOX10) and concurrent activation of TGF-β signaling in this process, but the molecular link between them has remained unresolved. Here, we identify a SOX10-miR-106a/363-TGFBR2 regulatory axis that governs adaptive resistance. SOX10 directly activates transcription of the miR-106a/363 cluster through a distal cis-regulatory element. In turn, the miR-106a/363 cluster members miR-106a-5p and miR-20b-5p suppress TGFBR2 post-transcriptionally, while miR-363-3p indirectly reduces TGFBR2 expression by targeting SOX4, a transcriptional activator of TGFBR2. This dual-layered repression restrains TGF-β signaling and maintains drug sensitivity. Loss of SOX10 diminishes miR-106a/363 expression, derepresses TGFBR2, and promotes a mesenchymal-like, drug-tolerant state. Restoring miR-106a/363 expression partially re-sensitizes melanomas to RAF inhibitors in vivo. These findings reveal a previously unrecognized regulatory circuit linking SOX10 to TGF-β signaling and highlight the miR-106a/363 cluster as a potential therapeutic target to overcome adaptive resistance in melanoma.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497353","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}

引用次数: 0

The expanding landscape of Deltex: signaling crosstalk and clinical implications. Deltex的扩展景观：信号串扰和临床意义。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-18 DOI: 10.1007/s00018-026-06353-4

Vartika Sharma, Pratikshya Sahoo, Mousumi Mutsuddi, Ashim Mukherjee

{"title":"The expanding landscape of Deltex: signaling crosstalk and clinical implications.","authors":"Vartika Sharma, Pratikshya Sahoo, Mousumi Mutsuddi, Ashim Mukherjee","doi":"10.1007/s00018-026-06353-4","DOIUrl":"10.1007/s00018-026-06353-4","url":null,"abstract":"The deltex (DTX) gene family encodes RING-type E3 ubiquitin ligases that are central to the regulation of the Notch signaling pathway, a mechanism governing cell fate, differentiation, proliferation, and apoptosis during development and adult tissue homeostasis. In Drosophila melanogaster, the Deltex (Dx) fine-tunes Notch signaling by modulating receptor endocytosis and degradation, acting as either an enhancer or a suppressor depending on the context. Insights from flies have revealed the evolutionary conservation of the Dx-Notch interaction across species, including humans. However, recent studies have expanded this view, identifying Dx as a regulator of multiple signaling pathways beyond Notch, specifically Wingless, Decapentaplegic, and Toll, underscoring its role as a hub for cellular communication. Through its broad regulatory network, Dx influences fundamental processes including cell growth, differentiation, apoptosis, and homeostasis. Dysregulation of Dx expression and function has been implicated in several diseases, ranging from cancer to immunological disorders and congenital abnormalities, positioning it as a promising therapeutic target. Despite these advances, important gaps remain in our understanding of Dx substrates, molecular mechanisms, and their full spectrum of physiological and pathological roles. Future research will be crucial to uncovering the broader biology of DTX family proteins and enabling their clinical application as diagnostic and prognostic markers. This review consolidates current knowledge and emerging insights on Dx, providing a framework to guide future research and therapeutic exploration.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497045","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}

引用次数: 0

Correction to: Knockdown of Foxg1 in supporting cells increases the trans‑differentiation of supporting cells into hair cells in the neonatal mouse cochlea. 修正：支持细胞中Foxg1的敲低增加了新生小鼠耳蜗支持细胞向毛细胞的反式分化。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-17 DOI: 10.1007/s00018-026-06289-9

Shasha Zhang, Yuan Zhang, Ying Dong, Lingna Guo, Zhong Zhang, Buwei Shao, Jieyu Qi, Han Zhou, Weijie Zhu, Xiaoqian Yan, Guodong Hong, Liyan Zhang, Xiaoli Zhang, Mingliang Tang, Chunjie Zhao, Xia Gao, Renjie Chai

引用次数: 0

Upregulation of PTPRO by WT1 alleviates podocyte injury in diabetic nephropathy through inhibiting the c-Abl/p53 pathway. WT1上调PTPRO通过抑制c-Abl/p53通路减轻糖尿病肾病足细胞损伤。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-17 DOI: 10.1007/s00018-026-06343-6

Hengjiang Guo, Li Wang, Yiru Tong, Yan Jiang, Xingmei Yao, Limin Lu, Rong Wei

{"title":"Upregulation of PTPRO by WT1 alleviates podocyte injury in diabetic nephropathy through inhibiting the c-Abl/p53 pathway.","authors":"Hengjiang Guo, Li Wang, Yiru Tong, Yan Jiang, Xingmei Yao, Limin Lu, Rong Wei","doi":"10.1007/s00018-026-06343-6","DOIUrl":"10.1007/s00018-026-06343-6","url":null,"abstract":"Podocyte injury plays a central role in the pathogenesis of diabetic nephropathy (DN). Protein tyrosine phosphatase receptor type O (PTPRO) has been implicated in glomerular disease, yet its specific role and regulatory mechanism in DN remain poorly understood. Here, we demonstrated that PTPRO expression was significantly downregulated in the glomeruli of DN mice and patients with DN, as well as in cultured podocytes exposed to diabetic stressors. Functional studies revealed that Ptpro knockdown induced podocyte injury, characterized by reduced Nephrin and Podocin expression, increased apoptosis, actin cytoskeleton disruption, enhanced migration, and reduced adhesion. Conversely, PTPRO overexpression ameliorated high glucose (HG)-induced podocyte damage. Mechanistically, PTPRO interacted with and dephosphorylated c-Abl, thereby suppressing the c-Abl/p53 signaling pathway. Pharmacological activation of c-Abl abolished the protective effects of PTPRO. Furthermore, we identified PTPRO as a direct transcriptional target of WT1, a podocyte master transcription factor downregulated in DN. WT1 overexpression restored PTPRO expression, suppressed c-Abl/p53 signaling, and ameliorated HG-induced podocyte injury in vitro. In vivo, podocyte-specific overexpression of WT1 via adeno-associated virus delivery in db/db mice attenuated proteinuria, glomerulosclerosis, and podocyte foot process effacement, accompanied by restored PTPRO expression and inhibition of the c-Abl/p53 pathway. Collectively, these findings establish that PTPRO functions downstream of WT1 to protect podocytes in DN by suppressing c-Abl/p53 signaling. Targeting the WT1-PTPRO-c-Abl-p53 axis may represent a novel therapeutic strategy for DN.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469279","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}

引用次数: 0

Vestibular hair cell redundancy and the critical requirement of type I cells for balance maintenance. 前庭毛细胞冗余和I型细胞维持平衡的关键要求。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-17 DOI: 10.1007/s00018-026-06348-1

Yikang Huang, Wenli Ni, Qin Zhou, Mingchuan Feng, Tao Jiang, Shunji He, Yan Chen, Wenyan Li

{"title":"Vestibular hair cell redundancy and the critical requirement of type I cells for balance maintenance.","authors":"Yikang Huang, Wenli Ni, Qin Zhou, Mingchuan Feng, Tao Jiang, Shunji He, Yan Chen, Wenyan Li","doi":"10.1007/s00018-026-06348-1","DOIUrl":"10.1007/s00018-026-06348-1","url":null,"abstract":"Vestibular hair cells (HCs) are sensory mechanotransducers essential for balance and spatial orientation, yet the relative contributions of HC number and subtype to vestibular function remain unresolved. Here, we developed a dose-dependent injury model in adult Pou4f3DTR mice by administering diphtheria toxin (DT), which induced selective HC ablation across vestibular organs. Both type I and type II HCs were lost following DT treatment. Type II HCs exhibited higher susceptibility to DT at lower doses, although this difference diminished as DT dose increased and overall HC survival declined. Functional analyses revealed that mice retaining ~ 30% of vestibular HCs-with preserved subtype proportions and neural innervation-exhibited normal balance, while ~ 50% residual HCs were sufficient to maintain intact vestibulo-ocular reflexes. To elucidate subtype-specific roles, we employed two type I HC-deficient models: 3,3'-iminodipropionitrile-induced injury and Gfi1Cre/Atoh1-OE mice. Comparative analyses revealed that type I HCs were essential for vestibular function. Together, these findings establish a reliable injury model, demonstrate functional redundancy within vestibular HCs, and underscore the critical role of type I HCs. These insights suggest that efforts to restore vestibular function through HC regeneration should prioritize generating functional type I HCs, not merely increasing the total HC count.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469308","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}

引用次数: 0

ENO3-mediated glycolytic reprogramming participates in β-glucan-induced dendritic cells activation and anti-tumor responses. eno3介导的糖酵解重编程参与β-葡聚糖诱导的树突状细胞活化和抗肿瘤反应。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-16 DOI: 10.1007/s00018-026-06350-7

Jun Ding, Yongzhe Hao, Meng Yuan, Jie Pan, Yewen Xie, Xiao Sun, Yongling Ning, Chunjian Qi

{"title":"ENO3-mediated glycolytic reprogramming participates in β-glucan-induced dendritic cells activation and anti-tumor responses.","authors":"Jun Ding, Yongzhe Hao, Meng Yuan, Jie Pan, Yewen Xie, Xiao Sun, Yongling Ning, Chunjian Qi","doi":"10.1007/s00018-026-06350-7","DOIUrl":"10.1007/s00018-026-06350-7","url":null,"abstract":"Dendritic cells (DCs) are key initiators of antitumor immunity, yet the metabolic drivers governing their activation remain incompletely defined. Here, we show that the fungal immunomodulator β-glucan induces robust immune-metabolic reprogramming in bone marrow-derived DCs (BMDCs), characterized by coordinated increases in glycolysis and tricarboxylic acid cycle activity. This metabolic shift is essential for BMDCs activation, as inhibition of glycolysis or oxidative metabolism diminishes β-glucan-induced costimulatory molecule expression, proinflammatory cytokine production and T-cell priming. Multi-omics profiling identifies enolase 3 (ENO3) as a key glycolytic regulator selectively upregulated by β-glucan. ENO3 knockdown reduces glycolytic flux, decreases mitochondrial ATP and ROS production, and consequently impairs BMDCs maturation and CD8⁺ T-cell responses. In DC-specific ENO3-knockout mice, ENO3 deficiency significantly compromises the antitumor efficacy of β-glucan, which characterized by accelerated tumor growth, impaired DCs activation, reduced CD8⁺ T-cell infiltration, and an immunosuppressive tumor milieu. These findings reveal ENO3 as a critical metabolic regulator linking β-glucan sensing to DC-mediated antitumor immunity.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469269","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}

引用次数: 0

Molecular mechanisms and translational implications in apoptosis, ferroptosis, pyroptosis, and cuproptosis of spermatogonial stem cells. 精原干细胞凋亡、铁下垂、焦下垂和铜下垂的分子机制及其翻译意义。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-16 DOI: 10.1007/s00018-026-06337-4

Feng Deng, Jianghong Xiang, Zuping He

{"title":"Molecular mechanisms and translational implications in apoptosis, ferroptosis, pyroptosis, and cuproptosis of spermatogonial stem cells.","authors":"Feng Deng, Jianghong Xiang, Zuping He","doi":"10.1007/s00018-026-06337-4","DOIUrl":"10.1007/s00018-026-06337-4","url":null,"abstract":"Spermatogonial stem cells (SSCs) are essential for male fertility because they form the cellular foundation for normal spermatogenesis. Here we address the regulatory mechanisms governing cell deaths of SSCs, e.g., apoptosis, ferroptosis, pyroptosis, and cuproptosis, including transcriptional and post-transcriptional regulation, RNA-binding proteins, and epigenetic modifications (e.g., non-coding RNAs). We systematically elucidate testicular microenvironment and signaling pathways in controlling SSC deaths, including mitochondrial signaling, death receptor signaling, PI3K/AKT/mTOR, MAPK, and WNT/β-catenin pathways. We also discuss the translational applications of targeting key pathways or remodeling the microenvironment to intervene in SSC deaths. We highlight the prospects and requirements to develop the advanced technologies, e.g., the long-term in vitro human primary SSC culture systems, single cell multi-omics, novel gene editing approaches with high safety and efficiency, and translating efficacy from basic research to clinical applications. The present review aims to provide new and overall insights into better understanding the molecular mechanisms underlying cell deaths of SSCs and the pathogenesis of non-obstructive azoospermia (NOA), which could offer novel strategies for precise treatment of male infertility.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469250","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}

引用次数: 0

Structural and biochemical characterization of a novel DinG containing an endonuclease domain. 含有核酸内切酶结构域的新型丁基化合物的结构和生化特性。

IF 6.5 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2026-07-15 DOI: 10.1007/s00018-026-06346-3

Shen Li, Tianwen Gao, Wanshan Hao, Hang Chen, Xiaolei Hu, Rong Qi, Cheng Chen, Kaiying Cheng

{"title":"Structural and biochemical characterization of a novel DinG containing an endonuclease domain.","authors":"Shen Li, Tianwen Gao, Wanshan Hao, Hang Chen, Xiaolei Hu, Rong Qi, Cheng Chen, Kaiying Cheng","doi":"10.1007/s00018-026-06346-3","DOIUrl":"10.1007/s00018-026-06346-3","url":null,"abstract":"DinG-like proteins are members of the XPD-family SF2 helicases and are widely distributed in bacteria, yet they exhibit remarkable diversity in domain architecture and biological function. A distinct subgroup of DinG homologs harboring an N-terminal PD-(D/E)XK-type nuclease domain, designated EndoDinGs, has remained uncharacterized. Here, we report the first structural and functional characterization of this subgroup using Finegoldia magna DinG (FmaDinG) as a representative example. FmaDinG displays Mn2+-preferred endonuclease activity together with Mg2+-dependent 5'-3' unidirectional helicase activity. We determined the crystal structure of the FmaDinG-ssDNA-ADPNP complex at 2.26 Å resolution. Structural and biochemical analyses reveal a direct role of the Arch domain in DNA engagement and suggest a gating mechanism within the nuclease domain that regulates DNA entry, a feature that may be specific to the EndoDinG subgroup. Key residues required for nuclease and helicase activities were identified by site-directed mutagenesis. Together, these results support a mechanistic model in which EndoDinGs such as FmaDinG function as coordinated nuclease-helicase machines for DNA processing.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444649","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}

引用次数: 0