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

Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis. CDK1 对 CENP-N 的动态磷酸化引导着有丝分裂过程中染色体的准确分离。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad041

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

{"title":"Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.","authors":"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","doi":"10.1093/jmcb/mjad041","DOIUrl":"10.1093/jmcb/mjad041","url":null,"abstract":"In mitosis, accurate chromosome segregation depends on the kinetochore, a supermolecular machinery 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 microscopic analyses of human CCAN structure, we investigated how dynamic phosphorylation of human CENP-N regulates accurate chromosome segregation. Our mass spectrometric analyses revealed mitotic phosphorylation of CENP-N by CDK1, which modulates the CENP-L-CENP-N interaction for accurate chromosome segregation and CCAN organization. Perturbation of CENP-N phosphorylation is shown to prevent proper chromosome alignment and activate the spindle assembly checkpoint. These analyses provide mechanistic insight into a previously undefined link between the centromere-kinetochore network and accurate chromosome segregation.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9742627","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

A targetable pathway to eliminate TRA-1-60+/TRA-1-81+ chemoresistant cancer cells. 消除 TRA-1-60+/TRA-1-81+ 化疗耐药癌细胞的靶向途径。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad039

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

{"title":"A targetable pathway to eliminate TRA-1-60+/TRA-1-81+ chemoresistant cancer cells.","authors":"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","doi":"10.1093/jmcb/mjad039","DOIUrl":"10.1093/jmcb/mjad039","url":null,"abstract":"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+ cells are chemoresistant compared to TRA-1-60-/TRA-1-81- cells. Transcriptome profiling identified UGT1A10, shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and chemoresistance. From a high-content chemical screen, we identified Cymarin, which downregulates UGT1A10, eliminates TRA-1-60/TRA-1-81 expression, and increases chemosensitivity both in vitro and in vivo. Finally, TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival, which highlights their potentiality for targeted therapy. Therefore, we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance, as well as a leading drug candidate to target this pathway.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9643966","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

Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma. 细胞 gp96 通过阻断肝细胞癌中 NR5A2 SUMOylation 和泛素化来上调 AFP 的表达。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad027

Liyuan Qian, Zhentao Liang, Zihao Wang, Jiuru Wang, Xin Li, Jingmin Zhao, Zihai Li, Lizhao Chen, Yongai Liu, Ying Ju, Changfei Li, Songdong Meng

{"title":"Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma.","authors":"Liyuan Qian, Zhentao Liang, Zihao Wang, Jiuru Wang, Xin Li, Jingmin Zhao, Zihai Li, Lizhao Chen, Yongai Liu, Ying Ju, Changfei Li, Songdong Meng","doi":"10.1093/jmcb/mjad027","DOIUrl":"10.1093/jmcb/mjad027","url":null,"abstract":"Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). 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 and in vivo evidence that heat shock protein gp96 promoted AFP expression at the transcriptional level in HCC. NR5A2 was identified as a key transcription factor for the AFP gene, and its stability was enhanced by gp96. A further mechanistic study by co-immunoprecipitation, GST pull-down, and molecular docking showed gp96 and the SUMO E3 ligase RanBP2 competitively binding to NR5A2 at the sites spanning from aa 507 to aa 539. The binding of gp96 inhibited SUMOylation, ubiquitination, and subsequent degradation of NR5A2. In addition, clinical analysis of HCC patients indicated that gp96 expression in tumors was positively correlated with serum AFP levels. Therefore, our study uncovered a novel mechanism that gp96 regulates the stability of its client proteins by directly affecting their SUMOylation and ubiquitination. These findings will help in designing more accurate AFP-based HCC diagnosis and progression monitoring approaches.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489721","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

Legionella pneumophila-mediated host posttranslational modifications. 嗜肺军团菌介导的宿主翻译后修饰。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad032

Yi Yang, Ligang Mei, Jing Chen, Xiaorong Chen, Zhuolin Wang, Lu Liu, Aimin Yang

{"title":"Legionella pneumophila-mediated host posttranslational modifications.","authors":"Yi Yang, Ligang Mei, Jing Chen, Xiaorong Chen, Zhuolin Wang, Lu Liu, Aimin Yang","doi":"10.1093/jmcb/mjad032","DOIUrl":"10.1093/jmcb/mjad032","url":null,"abstract":"Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease. During infections, L. pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host. Notably, certain effector proteins mediate posttranslational modifications (PTMs), serving as useful approaches exploited by L. pneumophila to modify host proteins. Some effectors catalyze the addition of host protein PTMs, while others mediate the removal of PTMs from host proteins. In this review, we summarize L. pneumophila effector-mediated PTMs of host proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, and ADP-ribosylation, as well as dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, and delipidation. We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10720952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9437511","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

PML-LRIF1 interactions form a novel link between promyelocytic leukemia bodies and centromeres. PML-LRIF1相互作用在早幼粒细胞白血病体和着丝粒之间形成了一种新的联系。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad038

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

引用次数: 0

Human umbilical cord-derived mesenchymal stem cells alleviate oxidative stress-induced islet impairment via the Nrf2/HO-1 axis. 人脐带间充质干细胞通过Nrf2/HO-1轴减轻氧化应激诱导的胰岛损伤。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad035

Peng Liu, Baige Cao, Yang Zhou, Huina Zhang, Congrong Wang

引用次数: 2

Blockade of TNF-α/TNFR2 signalling suppresses colorectal cancer and enhances the efficacy of anti-PD1 immunotherapy by decreasing CCR8+ T regulatory cells. 阻断TNF-α/TNFR2信号抑制结直肠癌癌症，并通过减少CCR8+T调节细胞来增强抗PD1免疫疗法的疗效。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-03 DOI: 10.1093/jmcb/mjad067

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

{"title":"Blockade of TNF-α/TNFR2 signalling suppresses colorectal cancer and enhances the efficacy of anti-PD1 immunotherapy by decreasing CCR8+ T regulatory cells.","authors":"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","doi":"10.1093/jmcb/mjad067","DOIUrl":"https://doi.org/10.1093/jmcb/mjad067","url":null,"abstract":"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 remains unclear. Here, we reveal that a high level of TNF-α in the colorectal cancer (CRC) microenvironment upregulates CCR8 expression in Tregs via the TNFR2/NF-κB signalling pathway and the FOXP3 transcription factor. Furthermore, in both anti-PD1-responsive and anti-PD1-unresponsive tumour models, PD1 blockade induced CCR8+ Treg infiltration. In both models, Tnfr2 depletion or TNFR2 blockade suppressed tumour progression by reducing CCR8+ Treg infiltration and thus augmented the efficacy of anti-PD1 therapy. Finally, we identified that TNFR2+CCR8+ Tregs but not total Tregs are positively correlated with adverse prognosis in CRC and gastric cancer. Our work reveals the regulatory mechanisms of CCR8 in Tregs and identifies TNFR2 as a promising target for immunotherapy.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482559","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

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 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-09-28 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":"https://doi.org/10.1093/jmcb/mjad058","url":null,"abstract":"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 cells (iPSCs) in response to telomere-internal DSBs. We engineered 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 DDR, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase, 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, we find neither evidence that HR causes extension of telomeres beyond their initial lengths, nor an apparent role for ZSCAN4 in this process. Rather, 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 damage.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Ypel5 regulates liver development and function in zebrafish. Ypel5调节斑马鱼的肝脏发育和功能。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-08-03 DOI: 10.1093/jmcb/mjad019

Yun Deng, Xiao Han, Huiqiao Chen, Chaoxian Zhao, Yi Chen, Jun Zhou, Hugues de The, Jun Zhu, Hao Yuan

{"title":"Ypel5 regulates liver development and function in zebrafish.","authors":"Yun Deng, Xiao Han, Huiqiao Chen, Chaoxian Zhao, Yi Chen, Jun Zhou, Hugues de The, Jun Zhu, Hao Yuan","doi":"10.1093/jmcb/mjad019","DOIUrl":"10.1093/jmcb/mjad019","url":null,"abstract":"YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5-/- mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9161416","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

Efficient non-viral delivery of macromolecules in human primary hematopoietic stem cells and lymphocytes. 人类原代造血干细胞和淋巴细胞中大分子的有效非病毒递送。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-08-03 DOI: 10.1093/jmcb/mjad018

Chuan-Ping Zhang, Hou-Yuan Qiu, Cai-Xiang Zhang, Yu-Ming Zhang, Yi-Zhou Zhang, Hao Yin, Ke-Qin Zhang, Ying Zhang

引用次数: 2