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

Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling. 发现 Trametinib 是细胞骨架波形蛋白重塑的协调者。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae009

Shuangshuang Zhao, Zhifang Li, Qian Zhang, Yue Zhang, Jiali Zhang, Gaofeng Fan, Xiaobao Cao, Yaming Jiu

{"title":"Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling.","authors":"Shuangshuang Zhao, Zhifang Li, Qian Zhang, Yue Zhang, Jiali Zhang, Gaofeng Fan, Xiaobao Cao, Yaming Jiu","doi":"10.1093/jmcb/mjae009","DOIUrl":"10.1093/jmcb/mjae009","url":null,"abstract":"The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions, including cell morphology, elasticity, migration, organelle localization, and resistance against mechanical or pathological stress. Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus. Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking, limiting in-depth studies on vimentin function and potential therapeutic applications. Here, we verified that a commercially available small molecule, trametinib, is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational regulation. Further evidence confirmed its low cytotoxicity and similar effects on different cell types. Importantly, Trametinib has no impact on the other two cytoskeletal systems, actin filaments and the microtubule network. Moreover, Trametinib regulates vimentin network dispersion rapidly and efficiently, with effects persisting for up to 48 h after drug withdrawal. We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin. In summary, we identified an unprecedented regulator Trametinib, which is capable of spreading the vimentin network toward the cell periphery, and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012715","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

Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern. 确定多种令人担忧的 SARS-CoV-2 变体所共有的药物对宿主的依赖性因素。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae004

Ilaria Frasson, Linda Diamante, Manuela Zangrossi, Elena Carbognin, Anna Dalla Pietà, Alessandro Penna, Antonio Rosato, Ranieri Verin, Filippo Torrigiani, Cristiano Salata, Marìa Paula Dizanzo, Lorenzo Vaccaro, Davide Cacchiarelli, Sara N Richter, Marco Montagner, Graziano Martello

{"title":"Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern.","authors":"Ilaria Frasson, Linda Diamante, Manuela Zangrossi, Elena Carbognin, Anna Dalla Pietà, Alessandro Penna, Antonio Rosato, Ranieri Verin, Filippo Torrigiani, Cristiano Salata, Marìa Paula Dizanzo, Lorenzo Vaccaro, Davide Cacchiarelli, Sara N Richter, Marco Montagner, Graziano Martello","doi":"10.1093/jmcb/mjae004","DOIUrl":"10.1093/jmcb/mjae004","url":null,"abstract":"The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants, some of which are resistant to vaccines and drugs targeting viral elements. Targeting host dependency factors, e.g. cellular proteins required for viral replication, would help prevent the development of resistance. However, it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host factors. To this end, we compared three variants of concern and found that the host transcriptional response was conserved, differing only in kinetics and magnitude. Clustered regularly interspaced short palindromic repeats screening identified host genes required for each variant during infection. Most of the genes were shared by multiple variants. We validated our hits with small molecules and repurposed the US Food and Drug Administration-approved drugs. All the drugs were highly active against all the tested variants, including new variants that emerged during the study (Delta and Omicron). Mechanistically, we identified reactive oxygen species production as a key step in early viral replication. Antioxidants such as N-acetyl cysteine (NAC) were effective against all the variants in both human lung cells and a humanized mouse model. Our study supports the use of available antioxidant drugs, such as NAC, as a general and effective anti-COVID-19 approach.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672024","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

Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression. 代谢组学分析显示，血清半胱氨酸水平在妊娠糖尿病进展过程中有所下降。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae010

Mengyu Lai, Jiaomeng Li, Jiaying Yang, Qingli Zhang, Yujia Gong, Yuhang Ma, Fang Fang, Na Li, Yingxiang Zhai, Tingting Shen, Yongde Peng, Jia Liu, Yufan Wang

{"title":"Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.","authors":"Mengyu Lai, Jiaomeng Li, Jiaying Yang, Qingli Zhang, Yujia Gong, Yuhang Ma, Fang Fang, Na Li, Yingxiang Zhai, Tingting Shen, Yongde Peng, Jia Liu, Yufan Wang","doi":"10.1093/jmcb/mjae010","DOIUrl":"10.1093/jmcb/mjae010","url":null,"abstract":"Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes, but its pathogenesis has not been clearly elucidated. Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression. Therefore, in the present study, we analysed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance throughout the three trimesters. We found that the variation trends of 38 metabolites were significantly changed during GDM development. Specifically, longitudinal analyses revealed that cysteine (Cys) levels significantly decreased over the course of GDM progression. Further study showed that Cys alleviated GDM in female mice at gestational day 14.5, possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis. Taken together, these findings suggest that the Cys metabolism pathway might play a crucial role in GDM and Cys supplementation represents a potential new treatment strategy for GDM patients.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012716","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 'Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer'. 关于 "LKB1突变型肺癌中腺癌向鳞癌转化驱动对KRAS抑制剂的耐药性 "的评论

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae013

Xinyuan Tong, Ningxia Zhang, Yun Xue, Hongbin Ji

引用次数: 0

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair. 人类诱导多能干细胞中的端粒DNA断裂触发ATR介导的阻滞和端粒酶非依赖性的端粒损伤修复。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjad058

Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson

{"title":"Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.","authors":"Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson","doi":"10.1093/jmcb/mjad058","DOIUrl":"10.1093/jmcb/mjad058","url":null,"abstract":"Although mechanisms of telomere protection are well-defined in differentiated cells, how stem cells sense and respond to telomere dysfunction, in particular telomeric double-strand breaks (DSBs), is poorly characterized. Here, we report the DNA damage signaling, cell cycle, and transcriptome changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase reverse transcriptase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length, which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099295","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

Regulation of m6Am RNA modification and its implications in human diseases. m6Am RNA修饰的调控及其对人类疾病的影响。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae012

Hao Jin, Zhouyuanjing Shi, Tianhua Zhou, Shanshan Xie

{"title":"Regulation of m6Am RNA modification and its implications in human diseases.","authors":"Hao Jin, Zhouyuanjing Shi, Tianhua Zhou, Shanshan Xie","doi":"10.1093/jmcb/mjae012","DOIUrl":"10.1093/jmcb/mjae012","url":null,"abstract":"N 6,2'-O-dimethyladenosine (m6Am) is a prevalent modification frequently found at the 5' cap-adjacent adenosine of messenger RNAs (mRNAs) and small nuclear RNAs (snRNAs) and the internal adenosine of snRNAs. This dynamic and reversible modification is under the regulation of methyltransferases phosphorylated CTD interacting factor 1 and methyltransferase-like protein 4, along with the demethylase fat mass and obesity-associated protein. m6Am RNA modification plays a crucial role in the regulation of pre-mRNA splicing, mRNA stability, and translation, thereby influencing gene expression. In recent years, there has been growing interest in exploring the functions of m6Am and its relevance to human diseases. In this review, we provide a comprehensive overview of the current knowledge concerning m6Am, with a focus on m6Am-modifying enzymes, sequencing approaches for its detection, and its impacts on pre-mRNA splicing, mRNA stability, and translation regulation. Furthermore, we highlight the roles of m6Am in the context of obesity, viral infections, and cancers, unravelling its underlying regulatory mechanisms.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175129","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 promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis. 极光 B 促进 CENP-T-CENP-W 相互作用，引导有丝分裂中染色体的准确分离。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae001

Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu

{"title":"Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis.","authors":"Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu","doi":"10.1093/jmcb/mjae001","DOIUrl":"10.1093/jmcb/mjae001","url":null,"abstract":"Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417352","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

Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered. 抗病毒因子及其对 HIV-1 的反作用：发现了许多，还有更多有待发现。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae005

Dorota Kmiec, Frank Kirchhoff

引用次数: 0

PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis. ZW10的PLK1磷酸化可引导有丝分裂中染色体的准确分离。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae008

Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang

{"title":"PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis.","authors":"Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang","doi":"10.1093/jmcb/mjae008","DOIUrl":"10.1093/jmcb/mjae008","url":null,"abstract":"Stable transmission of genetic information during cell division requires faithful chromosome segregation. Mounting evidence has demonstrated that polo-like kinase 1 (PLK1) dynamics at kinetochores control correct kinetochore-microtubule attachments and subsequent silencing of the spindle assembly checkpoint. However, the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive. Here, we identified a regulatory mechanism by which PLK1-elicited zeste white 10 (ZW10) phosphorylation regulates spindle checkpoint silencing in mitosis. ZW10 is a cognate substrate of PLK1, and the phosphorylation of ZW10 at Ser12 enables dynamic ZW10-Zwint1 interactions. Inhibition of ZW10 phosphorylation resulted in misaligned chromosomes, while persistent expression of phospho-mimicking ZW10 mutant caused premature anaphase, in which sister chromatids entangled as cells entered anaphase. These findings reveal the previously uncharacterized PLK1-ZW10 interaction through which dynamic phosphorylation of ZW10 fine-tunes accurate chromosome segregation in mitosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944219","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

Organization of microtubule plus-end dynamics by phase separation in mitosis. 通过有丝分裂中的相分离组织微管加端动力学

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae006

Fengrui Yang, Mingrui Ding, Xiaoyu Song, Fang Chen, Tongtong Yang, Chunyue Wang, Chengcheng Hu, Qing Hu, Yihan Yao, Shihao Du, Phil Y Yao, Peng Xia, Gregory Adams, Chuanhai Fu, Shengqi Xiang, Dan Liu, Zhikai Wang, Kai Yuan, Xing Liu

{"title":"Organization of microtubule plus-end dynamics by phase separation in mitosis.","authors":"Fengrui Yang, Mingrui Ding, Xiaoyu Song, Fang Chen, Tongtong Yang, Chunyue Wang, Chengcheng Hu, Qing Hu, Yihan Yao, Shihao Du, Phil Y Yao, Peng Xia, Gregory Adams, Chuanhai Fu, Shengqi Xiang, Dan Liu, Zhikai Wang, Kai Yuan, Xing Liu","doi":"10.1093/jmcb/mjae006","DOIUrl":"10.1093/jmcb/mjae006","url":null,"abstract":"In eukaryotes, microtubule polymers are essential for cellular plasticity and fate decisions. End-binding (EB) proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis. Here, we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid-liquid phase separation to compartmentalize the kinetochore-microtubule plus-end machinery, ensuring accurate kinetochore-microtubule interactions during chromosome segregation in mitosis. Perturbation of EB1-TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos. Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis, and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex, dissolves droplets in vitro, and harnesses accurate chromosome segregation. Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697731","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