Journal of Molecular Cell Biology最新文献_第2页

African swine fever virus DEAD-box helicase D1133L promotes OGG1-driven incision of genomic 8-oxoG via HDAC5 deacetylation. 非洲猪瘟病毒死箱解旋酶D1133L通过HDAC5去乙酰化促进ogg1驱动的基因组8-oxoG切割。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-08-27 DOI: 10.1093/jmcb/mjaf029

Jie Fan, Jifei Yang, Zhancheng Tian, Xiaoqiang Zhang, Shuxian Geng, Jianxun Luo, Istvan Boldogh, Qiaoying Zeng, Hong Yin, Guiquan Guan, Qingli Niu

{"title":"African swine fever virus DEAD-box helicase D1133L promotes OGG1-driven incision of genomic 8-oxoG via HDAC5 deacetylation.","authors":"Jie Fan, Jifei Yang, Zhancheng Tian, Xiaoqiang Zhang, Shuxian Geng, Jianxun Luo, Istvan Boldogh, Qiaoying Zeng, Hong Yin, Guiquan Guan, Qingli Niu","doi":"10.1093/jmcb/mjaf029","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf029","url":null,"abstract":"African swine fever virus (ASFV) infection induces oxidative stress and produces oxidative DNA damage bases, including 8-oxoguanine (8-oxoG). It is essential to promptly repair these damages to maintain genome stability. The enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) initiates the base excision repair (BER) pathway by recognizing and incising 8-oxoG and commonly regulates multiple biological processes by interacting with host and viral proteins. In this study, we elucidated the interaction between N-terminal region of ASFV DEAD-box helicase D1133L and OGG1, confirming the unique function of ASFV D1133L in DNA BER. Additionally, we demonstrated for the first time that ASFV D1133L is a substrate for the histone acetyltransferases CBP/p300 in the nucleus, while the deacetylation of D1133L via HDAC5, which primarily takes place in the cytoplasm by interacting with OGG1, markedly enhances the incision activity of OGG1 for 8-oxoG. Taken together, our findings unveil a previously undescribed role of ASFV D1133L in facilitating 8-oxoG incision by binding with OGG1 to safeguard genome integrity.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-08-26 DOI: 10.1093/jmcb/mjaf028

Wukun Ouyang, Jiaying Hao, Qiankun Niu, Eugene Douglass, Christian M Beusch, David E Gordon, Maggie Hall, Richard Moffit, 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 Douglass, Christian M Beusch, David E Gordon, Maggie Hall, Richard Moffit, Yuhong Du, Xiulei Mo","doi":"10.1093/jmcb/mjaf028","DOIUrl":"https://doi.org/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":5.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the ubiquitin-proteasome system and drug therapy in colorectal cancer. 靶向大肠癌泛素-蛋白酶体系统及药物治疗。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-08-22 DOI: 10.1093/jmcb/mjaf027

Ruixin Su, Yingying Shao, Qian Wang, Donghui Liu, Yitong Wang, Dexin Kong, Yuling Qiu

{"title":"Targeting the ubiquitin-proteasome system and drug therapy in colorectal cancer.","authors":"Ruixin Su, Yingying Shao, Qian Wang, Donghui Liu, Yitong Wang, Dexin Kong, Yuling Qiu","doi":"10.1093/jmcb/mjaf027","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf027","url":null,"abstract":"Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and the second leading cause of cancer-associated deaths, posing a significant threat to human health. Given the limited therapeutic options and poor prognosis associated with CRC, there is an urgent need to develop new targeted therapeutic strategies to enhance clinical outcomes. The ubiquitin-proteasome system (UPS), a central regulator for cellular protein homeostasis, plays a pivotal role in the initiation and progression of CRC. The UPS modulates several essential signaling pathways and is involved in regulating tumor immunity and resistance to chemotherapy. Thus, the UPS contributes significantly to the complex biological processes underlying CRC pathogenesis. In recent years, small-molecule compounds targeting the UPS have exhibited considerable therapeutic potential in CRC treatment. These drugs intervene in crucial steps in the UPS, such as the activity of E1, E2, and E3 enzymes, or directly target the proteasome, thereby regulating the degradation of oncogenic proteins and effectively impeding tumor progression. Moreover, emerging therapeutic strategies such as proteolysis-targeting chimera (PROTAC) and molecular glue technologies selectively degrade specific oncogenic proteins, thereby offering new avenues and promising opportunities for CRC treatment.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

egr1 and egr4 regulate zebrafish renal regeneration by promoting foxm1 expression. Egr1和egr4通过促进foxm1表达调节斑马鱼肾再生。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-08-15 DOI: 10.1093/jmcb/mjaf026

Xian He, Yuhua Sun

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 : 2025-08-13 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

RNA-Binding Protein Rbm38 as a Multifaceted Post-Transcriptional Regulator in Zebrafish Pancreatic Development. rna结合蛋白Rbm38在斑马鱼胰腺发育中的多面转录后调控作用

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-08-12 DOI: 10.1093/jmcb/mjaf025

Xiangmin Zhang, Xianpeng Li, Rui Liu, Lu Wang, Yunchao Wang, Ailong Zhang, Shuaiqi Yang, Hongyan Li

{"title":"RNA-Binding Protein Rbm38 as a Multifaceted Post-Transcriptional Regulator in Zebrafish Pancreatic Development.","authors":"Xiangmin Zhang, Xianpeng Li, Rui Liu, Lu Wang, Yunchao Wang, Ailong Zhang, Shuaiqi Yang, Hongyan Li","doi":"10.1093/jmcb/mjaf025","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf025","url":null,"abstract":"RNA-binding motif protein 38 (Rbm38), also known as RNPC1, is a major regulator of post-transcriptional gene expression. It represents a potential candidate gene linked to the susceptibility of type 2 diabetes, and decreased RBM38 expression can enhance the proliferation of pancreatic cancer cells in humans. However, its role in pancreatic development remains elusive. In this study, we explored the function of Rbm38 using zebrafish as a model. Pancreatic expression of Rbm38 is present at larval stages and is controlled by several transcription factors acting on specific rbm38 promoter regions. The loss of Rbm38 leads to abnormal pancreatic enlargement. Mechanistically, Rbm38 is involved in several aspects of post-transcriptional regulation of pancreatic gene expression. It destabilizes pdx1 transcripts by binding to the 3'-untranslated region and regulates alternative splicing of key pancreatic transcription factor genes, including isl1a, smad2, and nkx2.2a. These findings elucidate the role of Rbm38 in pancreatic development and highlight its significance in maintaining pancreatic homeostasis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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 : 2025-08-08 DOI: 10.1093/jmcb/mjaf023

Chenxi Hou, Fazhi Yu, Cheng Cao, Tianchen Wang, Zihang Pan, Minru 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, Minru Zhong, Xing Liu, Xuebiao Yao, Kaiguang Zhang, Zhenye Yang, Jing Guo","doi":"10.1093/jmcb/mjaf023","DOIUrl":"https://doi.org/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":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comments on 'Macrophages form dendrite-like pseudopods to enhance bacterial ingestion'. 巨噬细胞形成树突样伪足以增强细菌的摄食。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-31 DOI: 10.1093/jmcb/mjaf020

Changyuan Fan, Yaming Jiu

引用次数: 0

Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage. Wnt/β-catenin通路通过akap6介导的RyR2磷酸化和肌浆网钙渗漏诱导心功能障碍。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjaf002

Ang Li, Yuanyuan Shen, Zhenyan Li, Lin Li

{"title":"Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage.","authors":"Ang Li, Yuanyuan Shen, Zhenyan Li, Lin Li","doi":"10.1093/jmcb/mjaf002","DOIUrl":"10.1093/jmcb/mjaf002","url":null,"abstract":"The Wnt signaling pathway plays important roles in cardiomyocyte proliferation and cardiac regeneration after heart injury. Abnormal activation of the Wnt pathway causes a reduction in cardiomyocyte function, leading to hypertrophy, fibrosis, and heart failure. However, the mechanism through which Wnt signaling affects cardiomyocyte function during cardiac diseases is still unclear. In this study, we observed that activation of the Wnt/β-catenin pathway, but not the Wnt/Ca2+ pathway, leads to significant cytosol calcium enrichment. Such an effect can be inhibited by cycloheximide that blocks the downstream gene expression. By analyzing the transcriptome data, we found that activation of the Wnt/β-catenin pathway significantly upregulates the expression level of muscle-selective A kinase anchoring protein (mAKAP, also called AKAP6), a scaffold protein that can improve the interaction between protein kinase A (PKA) and its substrate ryanodine receptor 2 (RyR2) in cardiomyocytes. We further identified that AKAP6 is a target gene of the canonical Wnt pathway and increasing AKAP6 expression can enhance RyR2 phosphorylation by PKA, causing the sarcoplasmic reticulum calcium leakage and finally heart dysfunction. Our finding that the Wnt/β-catenin pathway affects cardiac calcium regulation via AKAP6 and RyR2 provides profound insights into heart diseases and sheds light on potential therapeutic strategies.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649326","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

Comments on 'Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages'. “巨噬细胞对细胞外基质的降解是由维门蛋白中间丝协调肌动蛋白应激纤维和足小体决定的”。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-07-28 DOI: 10.1093/jmcb/mjaf004

Sandrine Etienne-Manneville

引用次数: 0