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

Hypoxia signaling in the adipose tissue. 脂肪组织中的缺氧信号传导

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-03 DOI: 10.1093/jmcb/mjae039

Phu M Huynh, Fenfen Wang, Yu A An

引用次数: 0

HIV-1 inhibits IFITM3 expression to promote the infection of megakaryocytes. HIV-1 可抑制 IFITM3 的表达，从而促进巨核细胞的感染。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-01 DOI: 10.1093/jmcb/mjae042

Cyrine Bentaleb, Souad Adrouche, Jade Finkelstein, Christelle Devisme, Nathalie Callens, Claude Capron, Morgane Bomsel, Fernando Real

{"title":"HIV-1 inhibits IFITM3 expression to promote the infection of megakaryocytes.","authors":"Cyrine Bentaleb, Souad Adrouche, Jade Finkelstein, Christelle Devisme, Nathalie Callens, Claude Capron, Morgane Bomsel, Fernando Real","doi":"10.1093/jmcb/mjae042","DOIUrl":"https://doi.org/10.1093/jmcb/mjae042","url":null,"abstract":"Despite an undetectable plasma viral load as a result of antiretroviral therapy, HIV-1-infected individuals with poor immune reconstitution harbor infectious HIV-1 within their platelets. Megakaryocytes, as platelet precursors, are the likely cellular origin of these HIV-1-containing platelets. To investigate the mechanisms that allow megakaryocytes to support HIV-1 infection, we established in vitro models of viral infection using hematopoietic stem cell-derived megakaryocytes and the megakaryocytic MEG-01 cell line. We observed HIV-1 DNA provirus integration into the megakaryocyte cell genome, self-limiting virus production, and HIV-1 protein and RNA compartmentalization, which are hallmarks of HIV-1 infection in myeloid cells. In addition, following HIV-1 infection of megakaryocyte precursors, the expression of interferon-induced transmembrane protein 3 (IFITM3), an antiviral factor constitutively expressed in megakaryocytes, was inhibited in terminally differentiated HIV-1-infected megakaryocytes. IFITM3 knockdown in MEG-01 cells prior to infection led to enhanced HIV-1 infection, indicating that IFITM3 acts as an HIV-1 restriction factor in megakaryocytes. Together, these findings indicate that megakaryocyte precursors are susceptible to HIV-1 infection, leading to terminally differentiated megakaryocytes harboring virus in a process regulated by IFITM3. Megakaryocytes may thus constitute a neglected HIV-1 reservoir that warrants further study in order to develop improved antiretroviral therapies and to facilitate HIV-1 eradication.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361586","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

ATP promotes protein coacervation through conformational compaction. ATP 通过构象压实促进蛋白质共轭。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-01 DOI: 10.1093/jmcb/mjae038

Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong

引用次数: 0

The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells. FAcilitates 染色质转录复合物调节神经干细胞中糖酵解与氧化磷酸化的比例。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1093/jmcb/mjae017

Yuhan Lou, Litao Wu, Wanlin Cai, Huan Deng, Rong Sang, Shanshan Xie, Xiao Xu, Xin Yuan, Cheng Wu, Man Xu, Wanzhong Ge, Yongmei Xi, Xiaohang Yang

{"title":"The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.","authors":"Yuhan Lou, Litao Wu, Wanlin Cai, Huan Deng, Rong Sang, Shanshan Xie, Xiao Xu, Xin Yuan, Cheng Wu, Man Xu, Wanzhong Ge, Yongmei Xi, Xiaohang Yang","doi":"10.1093/jmcb/mjae017","DOIUrl":"10.1093/jmcb/mjae017","url":null,"abstract":"Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891908","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

Synergistic regulation of fusion pore opening and dilation by SNARE and synaptotagmin-1. SNARE 和 synaptotagmin-1 对融合孔开放和扩张的协同调控。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1093/jmcb/mjae011

Kaiju Li, Kaiyu Li, Jiaqi Fan, Xing Zhang, Chengyan Tao, Yijuan Xiang, Lele Cui, Hao Li, Minghan Li, Yanjing Zhang, Jia Geng, Ying Lai

{"title":"Synergistic regulation of fusion pore opening and dilation by SNARE and synaptotagmin-1.","authors":"Kaiju Li, Kaiyu Li, Jiaqi Fan, Xing Zhang, Chengyan Tao, Yijuan Xiang, Lele Cui, Hao Li, Minghan Li, Yanjing Zhang, Jia Geng, Ying Lai","doi":"10.1093/jmcb/mjae011","DOIUrl":"10.1093/jmcb/mjae011","url":null,"abstract":"Fusion pore opening is a transient intermediate state of synaptic vesicle exocytosis, which is highly dynamic and precisely regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and synaptotagmin-1 (Syt1). Yet, the regulatory mechanism is not fully understood. In this work, using single-channel membrane fusion electrophysiology, we determined that SNAREpins are important for driving fusion pore opening and dilation but incapable of regulating the dynamics. When Syt1 was added, the closing frequency of fusion pores significantly increased, while the radius of fusion pores mildly decreased. In response to Ca2+, SNARE/Syt1 greatly increased the radius of fusion pores and reduced their closing frequency. Moreover, the residue F349 in the C2B domain of Syt1, which mediates Syt1 oligomerization, was required for clamping fusion pore opening in the absence of Ca2+, probably by extending the distance between the two membranes. Finally, in Ca2+-triggered fusion, the primary interface between SNARE and Syt1 plays a critical role in stabilizing and dilating the fusion pore, while the polybasic region of Syt1 C2B domain has a mild effect on increasing the radius of the fusion pore. In summary, our results suggest that Syt1, SNARE, and the anionic membrane synergically orchestrate the dynamics of fusion pore opening in synaptic vesicle exocytosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039644","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

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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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

Unleashing the power of antigen-presenting neutrophils. 释放抗原递呈中性粒细胞的力量

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-09-16 DOI: 10.1093/jmcb/mjae034

Yingcheng Wu, Jiaqiang Ma, Qiang Gao

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