Journal of Molecular Cell Biology最新文献_第3页

Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities. 染色体三分裂：从异常有丝分裂到治疗机会的新兴十字路口。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1093/jmcb/mjae016

Umer Ejaz, Zhen Dou, Phil Y Yao, Zhikai Wang, Xing Liu, Xuebiao Yao

{"title":"Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.","authors":"Umer Ejaz, Zhen Dou, Phil Y Yao, Zhikai Wang, Xing Liu, Xuebiao Yao","doi":"10.1093/jmcb/mjae016","DOIUrl":"10.1093/jmcb/mjae016","url":null,"abstract":"Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome mis-segregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863118","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

Phase separation of hnRNPA1 and TERRA regulates telomeric stability. hnRNPA1 和 TERRA 的相分离调节端粒的稳定性。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-23 DOI: 10.1093/jmcb/mjae037

Ziyan Xu, Yongrui Liu, Fudong Li, Yi Yang, Hong Zhang, Xing Liu, Xin Xie, Xianjun Chen, Yunyu Shi, Liang Zhang

{"title":"Phase separation of hnRNPA1 and TERRA regulates telomeric stability.","authors":"Ziyan Xu, Yongrui Liu, Fudong Li, Yi Yang, Hong Zhang, Xing Liu, Xin Xie, Xianjun Chen, Yunyu Shi, Liang Zhang","doi":"10.1093/jmcb/mjae037","DOIUrl":"https://doi.org/10.1093/jmcb/mjae037","url":null,"abstract":"Telomeres are repetitive DNA sequences and associated protein complexes located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and is related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. HnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, worked coordinately and displaced replication protein A from telomeric ssDNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for over twenty years. Our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA. Through structural analysis, we identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase separation ability of hnRNPA1 and disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data revealed the molecular mechanism of the droplet formation of hnRNPA1 and TERRA and the possible function of the droplets for maintaining genomic stability.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307933","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

Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression. Temsirolimus 可抑制 FSP1 酶的活性，从而诱导铁变态反应，抑制肝癌的进展。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-23 DOI: 10.1093/jmcb/mjae036

Rui-Lin Tian, Tian-Xiang Wang, Zi-Xuan Huang, Zhen Yang, Kun-Liang Guan, Yue Xiong, Pu Wang, Dan Ye

{"title":"Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression.","authors":"Rui-Lin Tian, Tian-Xiang Wang, Zi-Xuan Huang, Zhen Yang, Kun-Liang Guan, Yue Xiong, Pu Wang, Dan Ye","doi":"10.1093/jmcb/mjae036","DOIUrl":"https://doi.org/10.1093/jmcb/mjae036","url":null,"abstract":"Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent accumulation of lipid peroxidation. While lipid radical elimination reaction catalyzed by glutathione peroxidase 4 (GPX4) is a major anti-ferroptosis mechanism, inhibiting this pathway pharmaceutically shows promise as an anti-tumor strategy. However, certain tumor cells exhibit redundancy in lipid radical elimination pathways, rendering them unresponsive to GPX4 inhibitors. In this study, we conducted screens across different cancer cell lines and FDA-approved drugs, leading to the identification of temsirolimus in combination with the GPX4 inhibitor RSL3 as a potent inducer of ferroptosis in liver cancer cells. Mechanistically, temsirolimus sensitized liver cancer cells to ferroptosis by directly binding to and inhibiting ferroptosis suppressor protein 1 (FSP1) enzyme. Notably, while temsirolimus is recognized as a potent mTOR inhibitor, its ferroptosis-inducing effect is primarily attributed to its inhibition of FSP1 rather than mTOR activity. By performing in vitro colony formation assays and in vivo tumor xenograft models, we demonstrated that the combination of temsirolimus and RSL3 effectively suppressed liver tumor progression. This tumoricidal effect was associated with increased lipid peroxidation and induction of ferroptosis. In conclusion, our findings underscore the potential of combining multi-target ferroptosis-inducing agents to circumvent resistance to ferroptosis in liver cancer cells and highlight temsirolimus as a promising FSP1 inhibitor and ferroptosis inducer, which also deserves further investigation in translational medicine.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307934","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

Probing centromere-kinetochore core complex CENP-L/M assembly using cenpemlin. 使用 cenpemlin 探测中心粒-着丝点核心复合体 CENP-L/M 的组装。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-06 DOI: 10.1093/jmcb/mjae035

Olanrewaju Ayodeji Durojaye, Fengrui Yang, Xinjiao Gao, Felix Aikhionbare, Liangyu Zhang, Xing Liu, Xuebiao Yao

引用次数: 0

Correction to: Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy. 更正为线粒体醛脱氢酶通过 GSK3β 介导的线粒体完整性保护和 Parkin 介导的有丝分裂，拯救糖尿病心肌病。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-04 DOI: 10.1093/jmcb/mjae032

引用次数: 0

PHLDA2 is critical for p53-mediated ferroptosis and tumor suppression. PHLDA2 对 p53 介导的铁变态反应和肿瘤抑制至关重要。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-29 DOI: 10.1093/jmcb/mjae033

Xin Yang, Wei Gu

引用次数: 0

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

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

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

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