Journal of Molecular Cell Biology最新文献_第9页

Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis. TGF-β-非依赖性SMAD4-NFATc1-STAT3调控轴的鉴定与表征

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-01-24 DOI: 10.1093/jmcb/mjaf028

Wukun Ouyang, Jiaying Hao, Qiankun Niu, Eugene F Douglass, Christian M Beusch, David E Gordon, Maggie Hall, Richard A Moffitt, Yuhong Du, Xiulei Mo

{"title":"Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.","authors":"Wukun Ouyang, Jiaying Hao, Qiankun Niu, Eugene F Douglass, Christian M Beusch, David E Gordon, Maggie Hall, Richard A Moffitt, Yuhong Du, Xiulei Mo","doi":"10.1093/jmcb/mjaf028","DOIUrl":"10.1093/jmcb/mjaf028","url":null,"abstract":"SMAD4, a central mediator of the TGF-β signaling pathway, plays a critical role in regulating cellular processes such as proliferation, differentiation, and apoptosis. While SMAD4's canonical functions within TGF-β signaling are well-established, its non-canonical, TGF-β-independent roles remain poorly understood, particularly in the context of disease biology. Here, we investigate SMAD4's TGF-β-independent functions by identifying and characterizing its protein-protein interaction network. Using pancreatic ductal adenocarcinoma as a model system, we performed a SMAD4-focused oncogenic protein-protein interaction mapping and uncovered a novel interaction between SMAD4 and NFATc1. We demonstrated that SMAD4 binds to NFATc1 in a phosphorylation-dependent but TGF-β-independent manner, sequestering NFATc1 in the cytoplasm and inhibiting its transcriptional activity. The absence of this interaction in SMAD4-deficient PDAC cells is associated with the activation of NFATc1 transcriptional programs and upregulation of STAT3 at both mRNA and protein levels. Pharmacological profiling revealed multiple STAT3 inhibitors with selective efficacy against SMAD4-deficient PDAC cells in vitro, highlighting a potential therapeutic vulnerability. These findings identify a previously uncharacterized SMAD4-NFATc1 regulatory complex and establish its biological significance in regulating NFATc1-driven transcriptional programs, such as STAT3, providing critical insights into SMAD4's TGF-β-independent functions and uncovering new opportunities for therapeutic intervention in SMAD4-deficient contexts.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957553","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

Aurora B maintains spherical shape of mitotic cells via simultaneously stabilizing myosin II and vimentin. Aurora B通过同时稳定肌凝蛋白II和波形蛋白维持有丝分裂细胞的球形。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-12-29 DOI: 10.1093/jmcb/mjaf023

Chenxi Hou, Fazhi Yu, Cheng Cao, Tianchen Wang, Zihang Pan, Mingru Zhong, Xing Liu, Xuebiao Yao, Kaiguang Zhang, Zhenye Yang, Jing Guo

{"title":"Aurora B maintains spherical shape of mitotic cells via simultaneously stabilizing myosin II and vimentin.","authors":"Chenxi Hou, Fazhi Yu, Cheng Cao, Tianchen Wang, Zihang Pan, Mingru Zhong, Xing Liu, Xuebiao Yao, Kaiguang Zhang, Zhenye Yang, Jing Guo","doi":"10.1093/jmcb/mjaf023","DOIUrl":"10.1093/jmcb/mjaf023","url":null,"abstract":"Cells round up when they enter mitosis and maintain this rounded morphology until they pass the spindle assembly checkpoint during anaphase. However, the mechanisms that regulate and maintain this transient spherical state remain unclear. In this study, we demonstrate that both astral microtubules and Aurora B kinase are required to maintain cortex stability during prometaphase. Simultaneous inhibition of astral microtubules and Aurora B leads to severe and continuous deformation of mitotic cells, resulting in micronuclei containing chromosomes after the cells exit mitosis. Mechanistically, active Aurora B kinase reduces the activity of myosin light chain kinase through phosphorylation, which in turn decreases the motor activity of myosin II. Additionally, Aurora B kinase regulates the distribution of actin at the cortex by phosphorylating the intermediate filament protein vimentin. Blocking these phosphorylation events disrupts the para-cortex localization of vimentin around the cortex and leads to the dislocalization of actin at the cortex. These regulatory effects occur in highly mobile cells expressing vimentin. In summary, we show that during mitosis, Aurora B kinase coordinates the interactions between microtubules, actin, and intermediate filaments to stabilize the cortex of rounded mitotic cells, ensuring the successful completion of mitosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835369","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

Dimerization of ACAP4 is essential for its function in cell migration. ACAP4的二聚化对其在细胞迁移中的功能至关重要。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-12-29 DOI: 10.1093/jmcb/mjaf024

Hongfei Ma, Jingjing He, Zhiyou Fang, Fangyuan Xiong, Xuannv Zhao, Dongmei Wang, Xiaoyu Song, Chuanhai Fu, Tetsuro Urushidani, Xuebiao Yao, Hongwu Qian, Xing Liu

引用次数: 0

FOXO1 enhances G6PD expression to promote cancer cell antioxidative capacity. FOXO1增强G6PD表达，促进癌细胞抗氧化能力。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-12-29 DOI: 10.1093/jmcb/mjaf021

Xianhong Zhang, Jie Zhang, Mengmeng Wei, Min Zhao, Xiaoxiong Wang, Yongfeng Hui, Dongdong Yuan, Zijiao Wang, Wei Wu, Peng Jiang, Yujiong Wang, Le Li

{"title":"FOXO1 enhances G6PD expression to promote cancer cell antioxidative capacity.","authors":"Xianhong Zhang, Jie Zhang, Mengmeng Wei, Min Zhao, Xiaoxiong Wang, Yongfeng Hui, Dongdong Yuan, Zijiao Wang, Wei Wu, Peng Jiang, Yujiong Wang, Le Li","doi":"10.1093/jmcb/mjaf021","DOIUrl":"10.1093/jmcb/mjaf021","url":null,"abstract":"Metabolic adaptability, controlled by transcription factors or oncogenes, is critical for the survival of cancer cells. However, the mechanism by which the transcription factor forkhead box protein O1 (FOXO1) regulates the proliferation and survival of malignant tumor cells under high levels of reactive oxygen species (ROS) remains poorly understood. Here, we found that FOXO1 endows cancer cells with the strong antioxidative capacity and rapid proliferation. By upregulating the expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, FOXO1 promotes the synthesis of nicotinamide adenine dinucleotide phosphate and ribose 5-phosphate and thus enhances the antioxidative and proliferative capabilities of cancer cells. Induction of G6PD expression in FOXO1-deficient cells mitigates tumor growth inhibition and alleviates ROS level elevation. These results establish a critical role of FOXO1 in the regulation of G6PD during the antioxidative and proliferative processes of cancer cells.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345613","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

Intraflagellar transport-associated CCDC92 is required for spermiogenesis and male fertility in mice. 鞭毛内转运相关的CCDC92是小鼠精子发生和雄性生育所必需的。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-12-29 DOI: 10.1093/jmcb/mjaf022

Yue Lu, Xirui Zi, Qian Lyu, Qingchao Li, Hanxiao Yin, Yinghao Wang, Qijun Chen, Bingkun Kang, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song

{"title":"Intraflagellar transport-associated CCDC92 is required for spermiogenesis and male fertility in mice.","authors":"Yue Lu, Xirui Zi, Qian Lyu, Qingchao Li, Hanxiao Yin, Yinghao Wang, Qijun Chen, Bingkun Kang, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song","doi":"10.1093/jmcb/mjaf022","DOIUrl":"10.1093/jmcb/mjaf022","url":null,"abstract":"The differentiation of a round spermatid into a streamlined sperm cell involves a series of remarkable morphological changes, such as sperm head shaping and flagellum formation. However, the underlying mechanism of spermatid shaping remains unclear. In this study, we find that CCDC92 deficiency in mice leads to severe abnormalities of the sperm head and flagellum and causes male infertility. Ultrastructural analyses of testicular elongating Ccdc92 knockout spermatids reveal severely deformed manchette structures. The manchette defects impair the subsequent sperm nucleus elongation and acrosome anchoring, resulting in misshapen rod-like nuclei and detached acrosomes. Molecularly, CCDC92 interacts with intraflagellar transport (IFT) complex components and colocalizes with IFT proteins at the manchette in developing spermatids. Quantitative proteomics further reveals the requirement of CCDC92 for proper flagellar distribution of axonemal microtubule inner proteins. Our findings demonstrate an essential role of CCDC92 in regulating spermatid shaping and provide novel insights into the pathology of male infertility.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723999","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: Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells. 修正：碎屑3b在哺乳动物细胞中以依赖于ezrin的方式促进紧密连接。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-11-11 DOI: 10.1093/jmcb/mjaf012

引用次数: 0

The disruption of COPII vesicles activates HSF-1 through SEC-23. COPII囊泡的破坏通过SEC-23激活HSF-1。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-11-11 DOI: 10.1093/jmcb/mjaf017

Zhidong He, Na Tang, Hao Liu, Xueqing Wang, Yue Yin, Chao Peng, Yidong Shen

引用次数: 0

The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement. 机械反应性染色体乘客复合体在限制下维持沟侵入。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-11-11 DOI: 10.1093/jmcb/mjaf019

Chenxin Wang, Jingjing Ding, Chao Wang, Maiyong Zhang, Junjie Wu, Bowen Chen, Hui Yang, Ting Gang Chew

{"title":"The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement.","authors":"Chenxin Wang, Jingjing Ding, Chao Wang, Maiyong Zhang, Junjie Wu, Bowen Chen, Hui Yang, Ting Gang Chew","doi":"10.1093/jmcb/mjaf019","DOIUrl":"10.1093/jmcb/mjaf019","url":null,"abstract":"Cells sense and respond to forces from neighbouring cells and the extracellular matrix during growth and division. When cells undergo mitosis in a confined environment like in the tumour environment, high compressive stress causes unstable cell cortex and prolonged mitosis. Confined mitotic cells frequently experience chromosome loss and multipolar division. How the cortical instability affects cytokinesis under confinement is unclear. Here, we show that confined mitotic cells undergo furrow ingression comparable to unconfined mitotic cells but are strongly reliant on Aurora B kinase, a catalytic subunit of the chromosomal passenger complex (CPC) for its completion. Mechanistically, the cortical pool of CPC via the scaffolding protein INCENP sustains Aurora B at the equatorial cortex to drive furrow ingression under confinement. We identified mechanoresponsive elements within the single alpha-helix domain of INCENP that maintain the cortical CPC at the equatorial cortex to promote furrow ingression in response to high compressive stress. Thus, the cortical INCENP not only binds to actin filaments but also mechanically responds to forces at the equatorial cortex to regulate the CPC during confined cytokinesis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690560","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

Beyond the ends: potential implications of telomeric repeat-containing RNA (TERRA) for CNS diseases. 超越终点：端粒重复序列RNA （TERRA）对中枢神经系统疾病的潜在影响。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-11-11 DOI: 10.1093/jmcb/mjaf013

Hadjer Namous, Raghu Vemuganti

引用次数: 0

Argon improves microglia-mediated hippocampal neuronal hyperexcitability to alleviate anxiety-like behaviors in mice. 氩改善小胶质细胞介导的海马神经元的高兴奋性以减轻小鼠的焦虑样行为。

IF 6 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-11-11 DOI: 10.1093/jmcb/mjaf006

Jie Cheng, Baiyang Zheng, Shusu Luo, Yuan Yuan, Xiaobo Wu, Zhenglin Jiang, Xia Li

{"title":"Argon improves microglia-mediated hippocampal neuronal hyperexcitability to alleviate anxiety-like behaviors in mice.","authors":"Jie Cheng, Baiyang Zheng, Shusu Luo, Yuan Yuan, Xiaobo Wu, Zhenglin Jiang, Xia Li","doi":"10.1093/jmcb/mjaf006","DOIUrl":"10.1093/jmcb/mjaf006","url":null,"abstract":"The role of inflammation in psychiatric disorders, such as anxiety, has gained increasing attention, with the hippocampus being identified as a key region involved in emotional regulation. Argon has been reported to alleviate the symptoms of psychiatric disorders; however, its underlying mechanism remains unclear. In this study, we found that argon significantly suppressed lipopolysaccharide-induced anxiety-like behaviors and attenuated hippocampal neuronal hyperexcitability in mice. By analyzing neuronal excitability following microglial depletion and subsequent repopulation, as well as assessing microglial morphology, we confirmed that microglia are key targets of inflammation and validated the inhibitory effects of argon. Electrophysiological studies and transcriptome sequencing revealed that argon inhibited the microglia-released inflammatory cytokines via the Toll-like receptor 4/nuclear factor-κB signaling pathway, thereby improving the excitability of hippocampal neurons. Collectively, this study provides evidence that the regulation of microglia may be the underlying mechanism by which argon ameliorates neuroinflammation-induced anxiety-like behaviors.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12604011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557190","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