Journal of Molecular Cell Biology最新文献_第10页

Effective therapy of the small-molecule cocktail 5SM on adult rat heart after ischemia-reperfusion injury. 小分子鸡尾酒5SM对成年大鼠心肌缺血再灌注损伤的治疗作用。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad034

Lixia Zheng, Yuanyuan Chen, Zhengyuan Wu, Xiaojun Zhu, Jing-Wei Xiong

引用次数: 0

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus. 在诊断肥胖症和糖尿病方面，靶向基因面板比全外显子组测序更具优势。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad040

Hairong Yu, Haoyong Yu, Rong Zhang, Danfeng Peng, Dandan Yan, Yunjuan Gu, Yuqian Bao, Weiping Jia, Hong Zhang, Cheng Hu

{"title":"Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus.","authors":"Hairong Yu, Haoyong Yu, Rong Zhang, Danfeng Peng, Dandan Yan, Yunjuan Gu, Yuqian Bao, Weiping Jia, Hong Zhang, Cheng Hu","doi":"10.1093/jmcb/mjad040","DOIUrl":"10.1093/jmcb/mjad040","url":null,"abstract":"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. The coverage of targeted gene panel sequencing was significantly higher than that of WES. The diagnostic yield in patients sequenced by the panel was 32.9% with subsequent WES leading to three additional diagnoses with two novel genes. In total, 178 variants in 83 genes were detected in 146 patients by targeted sequencing. Three of the 178 variants were missed by WES, although the WES-only approach had a similar diagnostic yield. For the 335 samples only receiving targeted sequencing, the diagnostic yield was 32.2%. In conclusion, taking into account the lower costs, shorter turnaround time, and higher quality of data, targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES. Therefore, this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.","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/PMC10847719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697132","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

BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes. 胰腺β细胞中的BRSK2促进高胰岛素血症耦合胰岛素抵抗，其基因变异与人类2型糖尿病有关。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad033

Rufeng Xu, Kaiyuan Wang, Zhengjian Yao, Yan Zhang, Li Jin, Jing Pang, Yuncai Zhou, Kai Wang, Dechen Liu, Yaqin Zhang, Peng Sun, Fuqiang Wang, Xiaoai Chang, Tengli Liu, Shusen Wang, Yalin Zhang, Shuyong Lin, Cheng Hu, Yunxia Zhu, Xiao Han

{"title":"BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes.","authors":"Rufeng Xu, Kaiyuan Wang, Zhengjian Yao, Yan Zhang, Li Jin, Jing Pang, Yuncai Zhou, Kai Wang, Dechen Liu, Yaqin Zhang, Peng Sun, Fuqiang Wang, Xiaoai Chang, Tengli Liu, Shusen Wang, Yalin Zhang, Shuyong Lin, Cheng Hu, Yunxia Zhu, Xiao Han","doi":"10.1093/jmcb/mjad033","DOIUrl":"10.1093/jmcb/mjad033","url":null,"abstract":"Brain-specific serine/threonine-protein kinase 2 (BRSK2) plays critical roles in insulin secretion and β-cell biology. However, whether BRSK2 is associated with human type 2 diabetes mellitus (T2DM) has not been determined. Here, we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population. BRSK2 protein levels are significantly elevated in β cells from T2DM patients and high-fat diet (HFD)-fed mice due to enhanced protein stability. Mice with inducible β-cell-specific Brsk2 knockout (βKO) exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions. Moreover, βKO mice are protected from HFD-induced hyperinsulinemia, obesity, insulin resistance, and glucose intolerance. Conversely, gain-of-function BRSK2 in mature β cells reversibly triggers hyperglycemia due to β-cell hypersecretion-coupled insulin resistance. Mechanistically, BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner. The enhanced basal insulin secretion drives insulin resistance and β-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 in β cells. These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay between β cells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions.","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/PMC10782904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840654","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

Large-scale data-driven and physics-based models offer insights into the relationships among the structures, dynamics, and functions of chromosomes. 大规模的数据驱动模型和基于物理学的模型为染色体的结构、动力学和功能之间的关系提供了洞察力。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad042

Cibo Feng, Jin Wang, Xiakun Chu

{"title":"Large-scale data-driven and physics-based models offer insights into the relationships among the structures, dynamics, and functions of chromosomes.","authors":"Cibo Feng, Jin Wang, Xiakun Chu","doi":"10.1093/jmcb/mjad042","DOIUrl":"10.1093/jmcb/mjad042","url":null,"abstract":"The organized three-dimensional chromosome architecture in the cell nucleus provides scaffolding for 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 genome function. Over the last two decades, rapid development of experimental methods has provided unprecedented data to characterize the hierarchical structures and dynamic properties of chromosomes. In parallel, these enormous data offer valuable opportunities for developing quantitative computational models. Here, we review a variety of large-scale polymer models developed to investigate the structures and dynamics of chromosomes. Different from the underlying modeling strategies, these approaches can be classified into data-driven ('top-down') and physics-based ('bottom-up') categories. We discuss their contributions to offering valuable insights into the relationships among the structures, dynamics, and functions of chromosomes and propose the perspective of developing data integration approaches from different experimental technologies and multidisciplinary theoretical/simulation methods combined with different modeling strategies.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9742628","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

Extracellular and intracellular functions of coiled-coil domain containing 3. 含盘旋卷曲结构域 3 的细胞外和细胞内功能。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI: 10.1093/jmcb/mjad037

Sara Omari, Hyemin Lee, Jieqiong Wang, Shelya X Zeng, Hua Lu

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

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

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