Journal of Molecular Cell Biology最新文献

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 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-11-25 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":"10.1093/jmcb/mjad067","url":null,"abstract":"The 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 revealed that a high level of TNF-α in the colorectal cancer (CRC) microenvironment upregulated CCR8 expression in Tregs via the TNFR2/NF-κB signalling pathway and the FOXP3 transcription factor. Furthermore, in both anti-programmed cell death protein 1 (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 were positively correlated with adverse prognosis in patients with 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":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-25","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

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 : 2024-11-25 DOI: 10.1093/jmcb/mjae034

Yingcheng Wu, Jiaqiang Ma, Qiang Gao

引用次数: 0

Molecular insights into AGS3's role in spindle orientation: a biochemical perspective. 从分子角度看 AGS3 在纺锤体定向中的作用：生化视角。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-11-23 DOI: 10.1093/jmcb/mjae049

Shi Yu, Jie Ji, Jingwei Weng, Zhijun Liu, Wenning Wang

{"title":"Molecular insights into AGS3's role in spindle orientation: a biochemical perspective.","authors":"Shi Yu, Jie Ji, Jingwei Weng, Zhijun Liu, Wenning Wang","doi":"10.1093/jmcb/mjae049","DOIUrl":"https://doi.org/10.1093/jmcb/mjae049","url":null,"abstract":"The intrinsic regulation of spindle orientation during asymmetric cell division depends on the evolutionarily conserved protein complex LGN (Pins)/NuMA (Mud)/Gα⋅GDP. While the role of LGN and its Drosophila orthologue Pins is well-established, the function of AGS3, the paralogue of LGN, in spindle orientation during cell division remains controversial. This study substantiates the contentious nature of AGS3's function through systematic biochemical characterizations. The results confirm the high conservation of AGS3 in its functional structural domains, similar to LGN, and its comparable ability to bind to partners including NuMA, Insc, and Gαi3⋅GDP. However, in contrast to LGN, AGS3 and the microtubule-binding protein NuMA are unable to form stable hetero-hexamers or higher-order oligomeric complexes that are pivotal for effective regulation of spindle orientation. It was found that this notable difference between AGS3 and LGN stems from the N-terminal sequence preceding the conserved TPR motifs, which spans ∼20 residues. Furthermore, our findings substantiate the disruptive effect of Insc on the oligomeric AGS3/NuMA complex, while showing no impact on the oligomeric LGN/NuMA complex. Consequently, Insc emerges as an additional regulatory factor that distinguishes the functional roles of AGS3 and LGN, leading to the impairment of AGS3's ability to actively reorient the mitotic spindle. These results elucidate the molecular basis underlying the observed functional disparity in spindle orientation between LGN and AGS3, providing valuable insights into the regulation of cell division at the molecular level.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695365","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

Increased serum β-hydroxybutyrate/acetoacetate ratio and aggravated histological liver inflammation in females with metabolic dysfunction-associated steatotic liver disease and polycystic ovary syndrome. 代谢功能障碍相关性脂肪性肝病和多囊卵巢综合征女性血清β-羟丁酸/乙酰乙酸比值升高，肝脏组织学炎症加重。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-30 DOI: 10.1093/jmcb/mjae048

Xiaopeng Zhu, Guligeina Aikebaier, Xilei Ban, Qingxia Huang, Hongmei Yan, Xinxia Chang, Xinyu Yang, Xiaoyang Sun, Huiru Tang, Hua Bian, Xin Gao, Mingfeng Xia

引用次数: 0

CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production. CCT6A通过抑制HIF-1α介导的乳酸生成减轻肺纤维化。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae021

Peishuo Yan, Kun Yang, Mengwei Xu, Miaomiao Zhu, Yudi Duan, Wenwen Li, Lulu Liu, Chenxi Liang, Zhongzheng Li, Xin Pan, Lan Wang, Guoying Yu

{"title":"CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production.","authors":"Peishuo Yan, Kun Yang, Mengwei Xu, Miaomiao Zhu, Yudi Duan, Wenwen Li, Lulu Liu, Chenxi Liang, Zhongzheng Li, Xin Pan, Lan Wang, Guoying Yu","doi":"10.1093/jmcb/mjae021","DOIUrl":"10.1093/jmcb/mjae021","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a lethal progressive fibrotic lung disease. The development of IPF involves different molecular and cellular processes, and recent studies indicate that lactate plays a significant role in promoting the progression of the disease. Nevertheless, the mechanism by which lactate metabolism is regulated and the downstream effects remain unclear. The molecular chaperone CCT6A performs multiple functions in a variety of biological processes. Our research has identified a potential association between CCT6A and serum lactate levels in IPF patients. Herein, we found that CCT6A was highly expressed in type 2 alveolar epithelial cells (AEC2s) of fibrotic lung tissues and correlated with disease severity. Lactate increases the accumulation of lipid droplets in epithelial cells. CCT6A inhibits lipid synthesis by blocking the production of lactate in AEC2s and alleviates bleomycin-induced pulmonary fibrosis in mice. In addition, our results revealed that CCT6A blocks HIF-1α-mediated lactate production by driving the VHL-dependent ubiquitination and degradation of HIF-1α and further inhibits lipid accumulation in fibrotic lungs. In conclusion, we propose that there is a pivotal regulatory role of CCT6A in lactate metabolism in pulmonary fibrosis, and strategies aimed at targeting these key molecules could represent potential therapeutic approaches for pulmonary fibrosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957738","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

Structure-specific nucleases in genome dynamics and strategies for targeting cancers. 基因组动态中的结构特异性核酸酶和针对癌症的策略。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae019

Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen

{"title":"Structure-specific nucleases in genome dynamics and strategies for targeting cancers.","authors":"Haitao Sun, Megan Luo, Mian Zhou, Li Zheng, Hongzhi Li, R Steven Esworthy, Binghui Shen","doi":"10.1093/jmcb/mjae019","DOIUrl":"10.1093/jmcb/mjae019","url":null,"abstract":"Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes. They widely vary in substrates, causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material. Through cellular evolution of prokaryotic to eukaryotic, nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates, including flaps, bubbles, and Holliday junctions. These special structural configurations are commonly found as intermediates in processes like DNA replication, repair, and recombination. The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells. In this article, we review their roles in various pathways, including Okazaki fragment maturation during DNA replication, end resection in homology-directed recombination repair of DNA double-strand breaks, DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage, and HIV life cycle. As the nucleases serve as key points for the DNA dynamics, cellular apoptosis, and cancer cell survival pathways, we discuss the efforts in the field in developing the therapeutic regimens, taking advantage of recently available knowledge of their diversified structures and functions.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876596","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

CSPP1 preserves quiescent microtubule functions by dual-end capping. CSPP1 通过双端封顶来保护静态微管功能

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae022

Marina Mapelli

引用次数: 0

Sympathetic nerve signals: orchestrators of mammary development and stem cell vitality. 交感神经信号：乳腺发育和干细胞活力的协调者。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1093/jmcb/mjae020

Zi Ye, Yu Xu, Mengna Zhang, Cheguo Cai

{"title":"Sympathetic nerve signals: orchestrators of mammary development and stem cell vitality.","authors":"Zi Ye, Yu Xu, Mengna Zhang, Cheguo Cai","doi":"10.1093/jmcb/mjae020","DOIUrl":"10.1093/jmcb/mjae020","url":null,"abstract":"The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development. Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied, the influence of neural signals, particularly those from the sympathetic nervous system, remains poorly understood. Here, using a mouse mammary gland model, we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development. Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty, adulthood, and pregnancy, accompanied by a reduction in mammary stem cell numbers. Through in vitro three-dimensional culture and in vivo transplantation analyses, we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration, while activation of sympathetic nervous signaling promotes these capacities. Mechanistically, sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling pathway. Collectively, our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity, offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comments on 'Obstructive sleep apnea syndrome exacerbates NASH progression via selective autophagy-mediated Eepd1 degradation'. 关于 "阻塞性睡眠呼吸暂停综合征通过选择性自噬介导的 Eepd1 降解加剧 NASH 进展 "的评论

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-18 DOI: 10.1093/jmcb/mjae043

Jie Xiong, Suzhen Chen, Junli Liu

引用次数: 0

Aurora B/AIR-2 regulates sister centromere resolution and CENP-A/HCP-3 organization to prevent merotelic attachments. 极光B/AIR-2调节姐妹中心粒的分辨和CENP-A/HCP-3的组织，以防止分生附着。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-10-16 DOI: 10.1093/jmcb/mjae045

Yue Wang, Charmaine Yan Yu Wong, Karen Wing Yee Yuen

{"title":"Aurora B/AIR-2 regulates sister centromere resolution and CENP-A/HCP-3 organization to prevent merotelic attachments.","authors":"Yue Wang, Charmaine Yan Yu Wong, Karen Wing Yee Yuen","doi":"10.1093/jmcb/mjae045","DOIUrl":"https://doi.org/10.1093/jmcb/mjae045","url":null,"abstract":"During cell division, the accurate capture of sister kinetochores that are built on the centromeres of chromosomes by microtubules emanating from opposite spindle poles governs faithful chromosome segregation. To ensure sister chromatids separate correctly, sister centromeres undergo resolution to achieve bi-polar orientation prior to microtubule attachments. Failure of centromere resolution increases the frequency of merotelic attachments, with microtubules from opposite poles attaching to the same sister kinetochore, causing lagging chromosome, aneuploidy, and even cancer progression. The Aurora B-mediated tension-sensing machinery to correct erroneous kinetochore-microtubule attachments has been well studied. However, preventative mechanisms to avoid merotelic attachments that occur in the earlier mitotic stage are poorly understood. In this study, we found that inactivation of mitotic kinase Aurora B/AIR-2 increases merotelic attachments in Caenorhabditis elegans. On one hand, Aurora B/AIR-2-deficient cells exhibited a delay in the occurrence of centromere resolution and a disruption in targeting condensin II components to chromatin. On the other hand, loss of Aurora B/AIR-2 results in an increased localization of centromeric proteins CENP-A/HCP-3 and M18BP1/KNL-2 as well as the kinetochore protein MIS-12 on chromatin, which may generate ectopic kinetochores causing erroneous attachments. To conclude, this study elucidated that Aurora B/AIR-2 regulates sister centromere resolution and CENP-A/HCP-3 deposition to actively prevent merotely and chromosome instability in cells.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467866","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