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Synergistic regulation of fusion pore opening and dilation by SNARE and synaptotagmin-1 J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-03-04 Kaiju Li, Kaiyu Li, Jiaqi Fan, Xing Zhang, Chengyan Tao, Yijuan Xiang, Lele Cui, Hao Li, Minghan Li, Yanjing Zhang, Jia Geng, Ying Lai
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
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Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-03-02 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
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 analyzed the metabolic
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Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-02-29 Shuangshuang Zhao, Zhifang Li, Qian Zhang, Yue Zhang, Jiali Zhang, Gaofeng Fan, Xiaobao Cao, Yaming Jiu
The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments network 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
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PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-02-25 Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang
Stable transmission of genetic information during cell division requires faithful chromosome segregation. Mounting evidence has demonstrated that PLK1 dynamics at kinetochores control correct kinetochore–microtubule attachments and subsequent silencing of the spindle checkpoint. However, the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive. Here, we identified
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CSPP1 stabilizes microtubules by capping both plus and minus ends J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-02-23 Zhikai Wang, Wenwen Wang, Shuaiyu Liu, Fengrui Yang, Xu Liu, Shasha Hua, Lijuan Zhu, Aoqing Xu, Donald L Hill, Dongmei Wang, Kai Jiang, Jennifer Lippincott-Schwartz, Xing Liu, Xuebiao Yao
Although the dynamic instability of microtubules (MTs) is fundamental to many cellular functions, quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics. However, how these free MT tips are stabilized remains poorly understood. Here, we report that centrosome and spindle pole protein 1 (CSPP1) caps and stabilizes both
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Organization of microtubule plus-end dynamics by phase separation in mitosis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-02-07 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
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
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Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-02-04 Dorota Kmiec, Frank Kirchhoff
Extensive studies on HIV-1 have led to the discovery of a variety of structurally and functionally diverse innate defense factors that target various steps of the retroviral replication cycle. Some of them, such as APOBEC3, tetherin, and SERINC5, are well established. Their importance is evident from the fact that HIV-1 uses its accessory proteins Vif, Vpu, and Nef to counteract them. However, the
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Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-02-02 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
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 resistance. However, it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same
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Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-01-23 Peter Zorn, Jaime Calvo Sánchez, Tala Alakhras, Barbara Schreier, Michael Gekle, Stefan Hüttelmaier, Marcel Köhn
Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants. However, it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative splicing. Hence, we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more detail. By using a combination
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Aurora B promotes the CENP-T–CENP-W interaction to guide accurate chromosome segregation in mitosis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-01-11 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
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
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The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development J. Mol. Cell Biol. (IF 5.5) Pub Date : 2024-01-03 Xiaozhen Song, Ruixing Hu, Yi Chen, Man Xiao, Hong Zhang, Shengnan Wu, Qing Lu
TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways, contributing to immune responses, tumor progression, and embryonic development. Somatic mutations within the coiled-coil (CC) domain and WD40 repeat domain of TRAF7 could cause brain tumors, while germline pathogenic mutations contribute to severe developmental abnormalities. However, the
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Morphomics via next-generation electron microscopy J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-27 Raku Son, Kenji Yamazawa, Akiko Oguchi, Mitsuo Suga, Masaru Tamura, Motoko Yanagita, Yasuhiro Murakawa, Satoshi Kume
The living body is composed of innumerable fine and complex structures. Although these structures have been studied in the past, a vast amount of information pertaining to them still remains unknown. When attempting to observe these ultra-structures, the use of electron microscopy (EM) has become indispensable. However, conventional EM settings are limited to a narrow tissue area, which can bias observations
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JunB condensation attenuates vascular endothelial damage under hyperglycemic condition J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-23 Xuxia Ren, Zexu Cui, Qiaoqiao Zhang, Zhiguang Su, Wei Xu, Jinhui Wu, Hao Jiang
Endothelial damage is the initial and crucial factor in the occurrence and development of vascular complications in diabetic patients, contributing to morbidity and mortality. Although hyperglycemia has been identified as a damaging effector, the detailed mechanisms remain elusive. In this study, identified by ATAC-seq and RNA-seq, JunB reverses the inhibition of proliferation and the promotion of
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Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR–Stat3/Akt pathway J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-18 Qiyao Liu, Manyun Li, Minli Sun, Ruyue Xin, Yushu Wang, Qin Chen, Xiang Gao, Zhaoyu Lin
Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice
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Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-07 Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou
Carbohydrate metabolism disorders (CMDs), such as diabetes, galactosemia, and mannosidosis, cause ciliopathy-like multiorgan defects. However, the mechanistic link of cilia to CMD complications is still poorly understood. Herein, we describe a significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols. Moreover, environmental
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Impaired dNKAP function drives genome instability and tumorigenic growth in Drosophila epithelia J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-07 Ting Guo, Chen Miao, Zhonghua Liu, Jingwei Duan, Yanbin Ma, Xiao Zhang, Weiwei Yang, Maoguang Xue, Qiannan Deng, Pengfei Guo, Yongmei Xi, Xiaohang Yang, Xun Huang, Wanzhong Ge
Mutations or dysregulated expression of NF-kappaB activating protein (NKAP) family genes have been found in human cancers. How NKAP family gene mutations promote tumor initiation and progression remains to be determined. Here, we characterized dNKAP, the Drosophila homolog of NKAP, and showed that impaired dNKAP function causes genome instability and tumorigenic growth in a Drosophila epithelial tumor
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Glycogen synthase kinase 3 signaling in neural regeneration in vivo J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-07 Jing Zhang, Shu-Guang Yang, Feng-Quan Zhou
Glycogen synthase kinase 3 (GSK3) signaling plays important and broad roles in regulating neural development in vitro and in vivo. Here, we reviewed recent findings of GSK3-regulated axon regeneration in vivo in both the peripheral and central nervous systems and discussed a few controversial findings in the field. Overall, current evidence indicates that GSK3β signaling serves as an important downstream
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The capsid revolution J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-01 Ian A Taylor, Ariberto Fassati
Lenacapavir, targeting the HIV-1 capsid, is the first-in-class antiretroviral drug recently approved for clinical use. The development of Lenacapavir is attributed to the remarkable progress in our understanding of the capsid protein made during the last few years. Considered little more than a component of the virus shell to be shed early during infection, capsid has been found to be a key player
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Sex- and age-specific associations between abdominal fat and non-alcoholic fatty liver disease: a prospective cohort study J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-12-01 Hongli Chen, Yuexing Liu, Dan Liu, Yebei Liang, Zhijun Zhu, Keqing Dong, Huating Li, Yuqian Bao, Jiarui Wu, Xuhong Hou, Weiping Jia
Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging-quantified areas of abdominal adipose tissue
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IDeAS: an interactive database for dysregulated alternative splicing in cancers across Chinese and western patients. J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-11-27 Hanwen Zhou,Liyun Yuan,Yuanhu Ju,Yue Hu,Siqi Wang,Ruifang Cao,Zefeng Wang,Guoqing Zhang
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Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-11-23 Zhi Zhong, Jiangchuan Du, Xiangjie Zhu, Lingting Guan, Yanyu Hu, Peilin Zhang, Hongyang Wang
Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods. However, these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes. In this study, we present a transgene-free, highly efficient chemical-induced direct reprogramming approach
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Targeting the PD-L1 cytoplasmic domain and its regulatory pathways to enhance cancer immunotherapy J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-11-23 Fangni Chai, Pan Li, Xin Liu, Zhihui Zhou, Haiyan Ren
As a significant member of the immune checkpoint, programmed cell death 1 ligand 1 (PD-L1) plays a critical role in cancer immune escape and has become an important target for cancer immunotherapy. Clinically approved drugs mainly target the extracellular domain of PD-L1. Recently, the small cytoplasmic domain of PD-L1 has been reported to regulate PD-L1 stability and function through multiple pathways
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A multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4–SMAD3–DNA complex J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-11-15 Wukun Ouyang, Qianjin Li, Qiankun Niu, Min Qui, Haian Fu, Yuhong Du, Xiulei Mo
The transforming growth factor-beta (TGFβ) signaling pathway plays crucial roles in the establishment of an immunosuppressive tumor microenvironment, making anti-TGFβ agents a significant area of interest in cancer immunotherapy. However, the clinical translation of current anti-TGFβ agents that target upstream cytokines and receptors remains challenging. Therefore, the development of small-molecule
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Blockade of TNF-α/TNFR2 signalling suppresses colorectal cancer and enhances the efficacy of anti-PD1 immunotherapy by decreasing CCR8+ T regulatory cells. J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-11-03 Yixian Guo,Feng Xie,Xu Liu,Shouyu Ke,Jieqiong Chen,Yi Zhao,Ning Li,Zeyu Wang,Gang Yi,Yanying Shen,Dan Li,Chunchao Zhu,Zizhen Zhang,Gang Zhao,Hong Lu,Bin Li,Wenyi Zhao
Enrichment of regulatory T cells (Tregs) in the tumour microenvironment (TME) has been recognized as one of the major factors in the initiation and development of resistance to immune checkpoint inhibitors. C-C motif chemokine receptor 8 (CCR8), a marker of activated suppressive Tregs, has a significant impact on the functions of Tregs in the TME. However, the regulatory mechanism of CCR8 in Tregs
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The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-26 Matthias Hamdorf, Thomas Imhof, Ben Bailey-Elkin, Janina Betz, Sebastian J Theobald, Alexander Simonis, Veronica Di Cristanziano, Lutz Gieselmann, Felix Dewald, Clara Lehmann, Max Augustin, Florian Klein, Miguel A Alejandre Alcazar, Robert Rongisch, Mario Fabri, Jan Rybniker, Heike Goebel, Jörg Stetefeld, Bent Brachvogel, Claus Cursiefen, Manuel Koch, Felix Bock
The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In response
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The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-24 Weiwei Qi, Zhenzhen Fang, Chuanghua Luo, Honghai Hong, Yanlan Long, Zhiyu Dai, Junxi Liu, Yongcheng Zeng, Ti Zhou, Yong Xia, Xia Yang, Guoquan Gao
Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the commonest causes for liver dysfunction. Adipose triglyceride lipase (ATGL) is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis. However, the expression and regulation of ATGL in NAFLD remain unclear. Herein, our results showed that ATGL protein
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Forty years of HIV research inspires the development of SARS-CoV-2 therapy. J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-23 Roberto Patarca,William A Haseltine
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Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-23 Yan Xu, Wentao Qi, Chengzu Zheng, Yuan Li, Zhiyuan Lu, Jianmin Guan, Chunhua Lu, Baobing Zhao
Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by the fusion gene BCR: ABL1. Drug resistance to tyrosine kinase inhibitors (TKIs) due to BCR: ABL1 mutation and residual leukemia stem cells (LSCs) remain major challenges for CML treatment. Here, we revealed the requirement of VDR in the progression of CML, in which VDR was upregulated by BCR: ABL1, accounting for its high expression
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Targeting dysregulated splicing factor in cancer: lessons learned from RBM10 deficiency J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-12 Yongbo Wang, Zefeng Wang
RNA splicing dysregulation is considered as a molecular hallmark and important therapeutic target of cancer. While targeting splicing has been intensively pursued for cancer therapy, specific modulators for dysregulated splicing factors are generally lacking. RNA binding motif protein 10 (RBM10) is frequently mutated in multiple cancers, in particular lung adenocarcinoma. Increasing evidence demonstrates
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SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-10 A Sofia F Oliveira, Deborah K Shoemark, Andrew D Davidson, Imre Berger, Christiane Schaffitzel, Adrian J Mulholland
The SARS-CoV-2 spike protein contains a functionally important fatty acid (FA) binding site, which is also found in some other coronaviruses, e.g. SARS-CoV and MERS-CoV. The occupancy of the FA site by linoleic acid (LA) reduces infectivity by ‘locking’ the spike in a less infectious conformation. Here, we use dynamical-nonequilibrium molecular dynamics (D-NEMD) simulations to compare the allosteric
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CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-10-02 Haixia Cheng, Lingyang Hua, Hailiang Tang, Zhongyuan Bao, Xiupeng Xu, Hongguang Zhu, Shuyang Wang, Zeyidan Jiapaer, Roma Bhatia, Ian F Dunn, Jiaojiao Deng, Daijun Wang, Shuchen Sun, Shihai Luan, Jing Ji, Qing Xie, Xinyu Yang, Ji Lei, Guoping Li, Xianli Wang, Ye Gong
Meningioma is one of the most common primary neoplasms in the central nervous system, whereas there is still no specific molecularly targeted therapy that has been approved for the clinical treatment of aggressive meningiomas. There is therefore an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up
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Sgo1 interacts with CENP-A to guide accurate chromosome segregation in mitosis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-29 Fengge Wu, Hameed Akbar, Chunyue Wang, Xiao Yuan, Zhen Dou, McKay Mullen, Liwen Niu, Liang Zhang, Jianye Zang, Zhikai Wang, Xuebiao Yao, Xiaoyu Song, Xing Liu
Shugoshin-1 (Sgo1) is necessary for maintaining sister centromere cohesion and ensuring accurate chromosome segregation during mitosis. It has been reported that the localization of Sgo1 at the centromere is dependent on Bub1-mediated phosphorylation of histone H2A at T120. However, it remains uncertain whether other centromeric proteins play a role in regulating the localization and function of Sgo1
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Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of Mitochondrial integrity and parkin-mediated mitophagy J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-29 Yingmei Zhang, Rongjun Zou, Miyesaier Abudureyimu, Qiong Liu, Jipeng Ma, Haixia Xu, Wei Yu, Jian Yang, Jianguo Jia, Sanli Qian, Haichang Wang, Yang Yang, Xin Wang, Xiaoping Fan, Jun Ren
Mitochondrial aldehyde dehydrogenase (ALDH2) offers proven cardiovascular benefit although its impact in diabetes remains elusive. This study examined the effect of ALDH2 overexpression (OE) and knockout (KO) on diabetic cardiomyopathy and mechanism involved with a focus on mitochondrial integrity. ALDH2 OE and KO mice were challenged with streptozotocin (STZ, 200 mg/kg. i.p.) to establish diabetes
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Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-29 Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson
Although mechanisms of telomere protection are well-defined in differentiated cells, it is poorly understood how stem cells sense and respond to telomere dysfunction. In particular, the broader impact of telomeric double-strand breaks (DSBs) in these cells is poorly characterized. Here, we report on DNA damage signaling, cell cycle, and transcriptome-level changes in human induced pluripotent stem
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ELP3 stabilizes c-myc to promote tumorigenesis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-27 Wentao Zhao, Cong Ouyang, Chen Huang, Jiaojiao Zhang, Qiao Xiao, Fengqiong Zhang, Huihui Wang, Furong Lin, Jinyang Wang, Zhanxiang Wang, Bin Jiang, Qinxi Li
ELP3, the catalytic subunit of Elongator complex, is an acetyltransferase and associated with tumor progression. However, the detail of ELP3 oncogenic function remains largely unclear. Here, we found that ELP3 stabilizes c-Myc to promote tumorigenesis in an acetyltransferase-independent manner. Mechanically, ELP3 competes with the E3-ligase FBXW7β for c-Myc binding, resulting in the inhibition of FBXW7β-mediated
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Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-27 Quanxin Jiang, Ning Wang, Sijia Lu, Jie Xiong, Yanmei Yuan, Junli Liu, Suzhen Chen
Non-alcoholic steatohepatitis (NASH) is a condition that progresses from non-alcoholic fatty liver disease (NAFLD) and is characterized by hepatic fat accumulation, inflammation, and fibrosis. It has the potential to lead to cirrhosis and liver cancer, with currently no effective pharmacological treatment available. In this study, we investigate the therapeutic potential of targeting ceruloplasmin
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A computational study for understanding the impact of p120-catenin on the cis-dimerization of cadherin J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-27 Zhaoqian Su, Vinh H Vu, Deborah E Leckband, Yinghao Wu
A prototype of cross-membrane signal transduction is that extracellular binding of cell surface receptors to their ligands induces intracellular signaling cascades. However, much less is known about the process in the opposite direction, called inside-out signaling. Recent studies show that it plays a more important role in regulating the functions of many cell surface receptors than we used to think
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SV2B defines a subpopulation of synaptic vesicles J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-09-08 Isabelle Paulussen, Hannes Beckert, Timothy F Musial, Lena J Gschossmann, Julia Wolf, Mathieu Schmitt, Jérôme Clasadonte, Georges Mairet-Coello, Christian Wolff, Susanne Schoch, Dirk Dietrich
Synaptic vesicles can undergo several modes of exocytosis, endocytosis, and trafficking within individual synapses, and their fates may be linked to differences in the vesicular protein composition. Here, we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy. SV2B is almost completely
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ANGPTL3 negatively regulates IL-1β-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-22 Yu Zhang, Zi-tong Zhang, Shi-yuan Wan, Jing Yang, Yu-juan Wei, Hui-jing Chen, Wan-zhu Zhou, Qiu-yi Song, Shu-xuan Niu, Ling Zheng, Kun Huang
Interleukin-1β (IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1β, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3)
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Regulation of endogenous retroviruses in murine embryonic stem cells and early embryos J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-22 Xinyi Lu
Endogenous retroviruses (ERVs) are an important component of the transposable elements, which constitute ∼50% of the mammalian genome. They exhibit dynamic expression during early embryonic development and are engaged in numerous biological processes. Therefore, their expression must be closely monitored by cells. Studies on the expression regulation of ERVs have been focused on mouse embryonic stem
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Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-16 Paweł Głodowicz, Konrad Kuczyński, Romain Val, André Dietrich, Katarzyna Rolle
Mutations in the small genome present in mitochondria often result in severe pathologies. Different genetic strategies have been explored, aiming to contribute to rescue such mutations. A number of these were based on the capacity of human mitochondria to import RNAs from the cytosol and were designed to repress the replication of the mutated genomes or to provide the organelles with wild-type versions
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CAMSAP2 and CAMSAP3 localize at microtubule intersections to regulate the spatial distribution of microtubules J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-12 Rui Zhang, Lusheng Gu, Wei Chen, Nobutoshi Tanaka, Zhengrong Zhou, Honglin Xu, Tao Xu, Wei Ji, Xin Liang, Wenxiang Meng
Microtubule networks support many cellular processes and have a highly ordered architecture. However, due to the limited axial resolution of conventional light microscopy, the structural features of these networks cannot be resolved in three-dimensional (3D) space. Here, we use customized ultra-high resolution interferometric single-molecule localization microscopy to characterize the microtubule networks
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Antibacterial activity of Lagerstreomia speciosa and its active compound, corosolic acid, enhances cefotaxime inhibitory activity against Staphylococcus aureus J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-05 Sylvia Sinelius, Jullietta Lady, Michellina Yunardy, Enty Tjoa, Agustina D R Nurcahyanti
Aims Various epidemiology studies have reported the emergence of Staphylococcus aureus and its methicillin resistance strain causing global health concerns, especially during and post-COVID-19 pandemic. This pathogen presents as a co-infection in patients with COVID-19. In addition, certain virulence factors and resistance to β-lactam antibiotics, including cefotaxime, have been identified. We aimed
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Development of microbial enrichments for simultaneous removal of sulfur and nitrogenous metabolites in saline water aquaculture J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-03 Prasanna Kumar Patil, Vinay Tharabenahalli Nagaraju, Viswanathan Baskaran, Satheesha Avunje, Rajesh R, Sudeep D Ghate, H G Solanki
Aim The aim of the study was to develop microbial enrichments from the nitrifying microbial consortia and the environment for simultaneous removal of ammonia, nitrate and sulfide in aquaculture systems at varied salinities. Methods and results Sulfur and nitrogen metabolites are the major factors affecting the farmed aquatic animal species and deteriorate the receiving environments causing ecological
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Distinct roles of the two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA Pol II transcription elongation J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-02 Zhuanzhuan Che, Xiaoxu Liu, Qian Dai, Ke Fang, Chenghao Guo, Junjie Yue, Haitong Fang, Peng Xie, Zhuojuan Luo, Chengqi Lin
The super elongation complex (SEC) containing P-TEFb plays a critical role in regulating transcription elongation. AFF1 and AFF4, members of the AF4/FMR2 family, act as central scaffold proteins of SEC and are associated with various human diseases. However, their precise roles in transcriptional control remain unclear. We here reveal differences in the genomic distribution patterns of AFF1 and AFF4
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The transcriptional activator Klf5 recruits p300-mediated H3K27ac for maintaining trophoblast stem cell pluripotency J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-08-01 Chengli Dou, Linhui Wu, Jingjing Zhang, Hainan He, Tian Xu, Zhisheng Yu, Peng Su, Xia Zhang, Junling Wang, Yi-Liang Miao, Jilong Zhou
The effective proliferation and differentiation of trophoblast stem cells (TSCs) is indispensable for the development of the placenta, which is the key to maintaining normal fetal growth during pregnancy. Kruppel-like factor 5 (Klf5) is implicated in the activation of pluripotent gene expression in embryonic stem cells (ESCs), yet its function in TSCs is poorly understood. Here, we show that Klf5 knockdown
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Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells. J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-07-25 Jing Wen,Jing Sun,Yanhong Tang,Jincun Zhao,Xiao Su
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Stability and function of RCL1 are dependent on interaction with BMS1 J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-07-15 Yong Wang, Zhenyu Zhao, Hongyan Yu, Hui Shi, Boxiang Tao, Yinan He, Jun Chen, Jinrong Peng, Meifu Gan, Li Jan Lo
During ribosome biogenesis, the small subunit (SSU) processome is responsible for 40S assembly. The BMS1/RCL1 complex is a core component of SSU processome that plays an important role in 18S rRNA processing and maturation. Genetic studies using zebrafish mutants indicate that both Bms1l (Bms1-like) and Rcl1 are essential for digestive organs development. In spite of the vital functions of this complex
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Estrogen receptor α-mediated signaling inhibits type I interferon response to promote breast cancer J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-07-14 Li-Bo Cao, Zi-Lun Ruan, Yu-Lin Yang, Nian-Chao Zhang, Chuan Gao, Cheguo Cai, Jing Zhang, Ming-Ming Hu, Hong-Bing Shu
Estrogen receptor α (ERα) is an important driver and therapeutic target in approximately 70% of breast cancers. How ERα drives breast carcinogenesis is not fully understood. In this study, we show that ERα is a negative regulator of type I interferon (IFN) response, which is critical for breast carcinogenesis. Activation of ERα by its natural ligand estradiol inhibits IFN-β-induced transcription of
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Transcriptional pausing induced by ionizing radiation enables the acquisition of radioresistance in nasopharyngeal carcinoma J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-07-06 Honglu Liu, Huanyi Fu, Chunhong Yu, Na Zhang, Canhua Huang, Lu Lv, Chunhong Hu, Fang Chen, Zhiqiang Xiao, Zhuohua Zhang, Huasong Lu, Kai Yuan
Lesions on the DNA template can impact transcription via distinct regulatory pathways. Ionizing radiation (IR) as the mainstay modality for many malignancies elicits most of the cytotoxicity by inducing a variety of DNA damages in the genome. How the IR treatment alters transcription cycle and whether it contributes to the development of radioresistance remain poorly understood. Here, we report an
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ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-06-29 Xueyao Ma, Mengyuan Li, Yi Liu, Xuefang Zhang, Xiaoyun Yang, Yun Wang, Yipeng Li, Jiayue Wang, Xiuhua Liu, Zhenzhen Yan, Xiaochun Yu, Chen Wu
Mono-ADP-ribosylation is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, mono-ADP-ribosylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin like (ARTCs) and ART diphtheria toxin like (ARTDs, also known
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Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-06-27 Ran Liu, Zhen Dou, Tian Tian, Xinjiao Gao, Lili Chen, Xiao Yuan, Chunyue Wang, Jiahe Hao, Ping Gui, McKay Mullen, Felix Aikhionbare, Liwen Niu, Guoqiang Bi, Peng Zou, Xuan Zhang, Chuanhai Fu, Xuebiao Yao, Jianye Zang, Xing Liu
In mitosis, accurate chromosome segregation depends on super-molecular machinery kinetochore that couples dynamic spindle microtubules to centromeric chromatin. However, the structure-activity relationship of the constitutive centromere-associated network (CCAN), during mitosis remains uncharacterized. Building on our recent cryo-electron microscopy structure of human CCAN, here we reveal the molecular
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Large-scale data-driven and physics-based models offer insights into the relationships among the structures, dynamics, and functions of the chromosomes J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-06-25 Cibo Feng, Jin Wang, Xiakun Chu
The organized three-dimensional chromosome architecture in the cell nucleus provides the scaffolding for the precise regulation of gene expression. When the cell changes its identity in the cell fate decision-making process, extensive rearrangements of chromosome structures occur accompanied by large-scale adaptations of gene expression, underscoring the importance of chromosome dynamics in shaping
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A Targetable Pathway to Eliminate TRA-1-60+/TRA-1-81+ Chemoresistant Cancer Cells J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-06-16 Lei Tan, Xiaohua Duan, Pratyusha Mutyala, Ting Zhou, Sadaf Amin, Tuo Zhang, Brian Herbst, Gokce Askan, Tomer Itkin, Zhaoying Xiang, Fabrizio Michelassi, Michael D Lieberman, Christine A Iacobuzio-Donahue, Steven D Leach, Todd Evans, Shuibing Chen
Chemoresistance is a primary cause of treatment failure in pancreatic cancer. Identifying cell surface markers specifically expressed in chemoresistant cancer cells (CCCs) could facilitate targeted therapies to overcome chemoresistance. We performed an antibody-based screen and found that TRA-1–60 and TRA-1–81, two ‘stemness’ cell surface markers, are highly enriched in CCCs. Furthermore, TRA-1–60+/TRA-1–81+
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Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-06-16 Hairong Yu, Haoyong Yu, Rong Zhang, Danfeng Peng, Dandan Yan, Yunjuan Gu, Yuqian Bao, Weiping Jia, Hong Zhang, Cheng Hu
A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause. Here, we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes. We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing (WES) data available for 146 of these patients
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PML-LRIF1 interactions form a novel link between promyelocytic leukemia bodies and centromeres. J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-11-27 Junying Li,Xiao Yuan,Fengrui Yang,Jun Cao,Chunyue Wang,Saima Akram,Peng Zou,Felix Aikhionbare,Xuejun Li,Yong Chen,Liangyu Zhang,Chuanhai Fu,Zhikai Wang,Xing Liu,Xuebiao Yao
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Extracellular and intracellular functions of coiled-coil domain containing 3 J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-06-02 Sara Omari, Hyemin Lee, Jieqiong Wang, Shelya X Zeng, Hua Lu
Coiled-coil domain containing 3 (CCDC3, also called favine) is a highly conserved protein initially identified as a protein secreted from adipocytes and endothelial cells (ECs) in the vascular system with endocrine-like functions. Recently, CCDC3 was also found to function as a nuclear tumor suppressor in breast cancers (BrCs). Although it is still understudied, CCDC3, since its discovery, has been
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A bacterial effector SidN/Lpg1083 promotes cell death by targeting Lamin-B2 J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-05-31 Jiajia Gao, Wenwen Xu, Feng Tang, Minrui Xu, Qin Zhou, Xingyuan Yang, Nannan Zhang, Jinming Ma, Qi Yang, Xiaofang Chen, Ximing Qin, Honghua Ge
To facilitate its survival, replication, and dissemination, the intracellular pathogen Legionella pneumophila relies on its unique Type IVB secretion system (T4SS) to deliver over 330 effectors to hijack host cell pathways in a spatiotemporal manner. The underlying mechanisms of the effectors and their host targets are largely unexplored due to their little sequence identity to known proteins and functional
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Human umbilical cord-derived mesenchymal stem cells alleviate oxidative stress-induced islet impairment via the Nrf2/HO-1 axis J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-05-28 Peng Liu, Baige Cao, Yang Zhou, Huina Zhang, Congrong Wang
Hyperglycaemia-induced oxidative stress may disrupt insulin secretion and β-cell survival in diabetes mellitus by overproducing reactive oxygen species. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) exhibit anti-oxidant properties. However, the mechanisms by which hUC-MSCs protect β-cells from high glucose-induced oxidative stress remain underexplored. In this study, we showed that
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Cellular gp96 upregulates AFP expression by blockade of NR5A2 SUMOylation and ubiquitination in HCC J. Mol. Cell Biol. (IF 5.5) Pub Date : 2023-05-19 Liyuan Qian, Zhentao Liang, Zihao Wang, Jiuru Wang, Xin Li, Jingmin Zhao, Zihai Li, Lizhao Chen, Yongai Liu, Ying ju, Changfei Li, Songdong Meng
AFP is the most widely used biomarker for the diagnosis of hepatocellular carcinoma. However, a substantial proportion of HCC patients have either normal or marginally increased AFP levels in serum, and the underlying mechanisms are not fully understood. In the present study, we provided in vitro as well as in vivo evidence that heat shock protein gp96 promoted AFP expression at the transcriptional