Cell insight最新文献_第3页

Replication-coupled inheritance of chromatin states 染色质状态的复制耦合遗传

Cell insight Pub Date : 2024-08-23 DOI: 10.1016/j.cellin.2024.100195

Aoqun Song , Yunting Wang , Cuifang Liu , Juan Yu , Zixu Zhang , Liting Lan , Haiyan Lin , Jicheng Zhao , Guohong Li

引用次数: 0

The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK 甲基转移酶 SETD3 通过与 hnRNPK 相互作用调节 mRNA 的替代剪接

Cell insight Pub Date : 2024-08-23 DOI: 10.1016/j.cellin.2024.100198

Yue-Yu Kong , Wen-Jie Shu , Shuang Wang , Zhao-Hong Yin , Hongguo Duan , Ke Li , Hai-Ning Du

{"title":"The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK","authors":"Yue-Yu Kong , Wen-Jie Shu , Shuang Wang , Zhao-Hong Yin , Hongguo Duan , Ke Li , Hai-Ning Du","doi":"10.1016/j.cellin.2024.100198","DOIUrl":"10.1016/j.cellin.2024.100198","url":null,"abstract":"<div><div>The methyltransferase SETD3 is an enzyme essential for catalyzing histidine-73 methylation on β-Actin, thereby promoting its polymerization and regulating muscle contraction. Although increasing evidence suggests that SETD3 is involved in multiple physiological or pathological events, its biological functions remain incompletely understood. In this study, we utilize <em>in situ</em> proximity labeling combined with mass spectrometry analysis to detect potential interacting partners of SETD3. Unexpectedly, we find that many splicing factors are associated with SETD3. Genome-wide RNA sequencing reveals that SETD3 regulates pre-mRNA splicing events, predominantly influencing exon skipping. Biochemical and bioinformatic analyses suggest that SETD3 interacts with hnRNPK, and they collaboratively regulate exon skipping in a common subset of genes. Functionally, we demonstrate that SETD3 and hnRNPK are required for retention of exon 7 skipping in the <em>FNIP1</em> gene. This promotes FNIP1-mediated nuclear translocation of the transcription factor TFEB and the subsequent induction of lysosomal and mitochondrial biogenesis. Overall, this study uncovers a novel function of SETD3 in modulating mRNA exon splicing.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 6","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000531/pdfft?md5=8b6985f58020f0031dd373c4d8c1f1d7&pid=1-s2.0-S2772892724000531-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of TBK1 activation in cancer cells 癌细胞中 TBK1 的激活机制

Cell insight Pub Date : 2024-08-22 DOI: 10.1016/j.cellin.2024.100197

Lianxin Hu , Qing Zhang

{"title":"Mechanism of TBK1 activation in cancer cells","authors":"Lianxin Hu , Qing Zhang","doi":"10.1016/j.cellin.2024.100197","DOIUrl":"10.1016/j.cellin.2024.100197","url":null,"abstract":"<div><p>TANK-binding kinase 1 (TBK1) is a serine/threonine kinase with well-established roles as a central player in innate immune signaling. Dysregulation of TBK1 activity has been implicated in a variety of pathophysiologic conditions, including cancer. Generally, TBK1 acts as an oncogene and increased TBK1 activity, indicated by increased phosphorylation at the Ser172 residue, can be observed in multiple human cancers. TBK1 can be activated either by autophosphorylation of Ser172 or transphosphorylation at this site by upstream kinases. Serving as a hub for integrating numerous extracellular and intracellular signals, TBK1 can be activated through multiple signaling pathways. However, the direct upstream kinase responsible for TBK1 activation remains elusive, which limits our comprehensive understanding of its activation mechanism and potential therapeutic application targeting TBK1-related signaling especially in cancer. In this review, we summarize the findings on mechanisms of TBK1 activation in cancer cells and recent discoveries that shed light on the direct upstream kinases promoting TBK1 activation.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277289272400052X/pdfft?md5=9b199a79a3184dac2c0896a6b04f770f&pid=1-s2.0-S277289272400052X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Finding new roles of classic biomolecular condensates in the nucleus: Lessons from fission yeast 寻找细胞核中经典生物分子凝聚物的新作用：裂变酵母的启示

Cell insight Pub Date : 2024-08-05 DOI: 10.1016/j.cellin.2024.100194

Tomoyasu Sugiyama

引用次数: 0

Cover 封面

Cell insight Pub Date : 2024-08-01 DOI: 10.1016/S2772-8927(24)00042-7

引用次数: 0

Role of the CARD8 inflammasome in HIV pathogenesis CARD8 炎症体在艾滋病毒发病机制中的作用

Cell insight Pub Date : 2024-07-19 DOI: 10.1016/j.cellin.2024.100193

Qiankun Wang , Liang Shan

{"title":"Role of the CARD8 inflammasome in HIV pathogenesis","authors":"Qiankun Wang , Liang Shan","doi":"10.1016/j.cellin.2024.100193","DOIUrl":"10.1016/j.cellin.2024.100193","url":null,"abstract":"<div><p>Human immunodeficiency virus (HIV) continues to be a significant global health challenge despite decades of research and advances in treatment. Substantial gaps in our understanding of the mechanisms of HIV pathogenesis and the host immune responses still exist. The interaction between HIV and these immune responses is pivotal in the disease progression to acquired immunodeficiency syndrome (AIDS). Recently, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome has emerged as a crucial factor in orchestrating innate immune responses to HIV infection and exerting a substantial impact on viral pathogenesis. CARD8 restricts viral replication by detecting the activity of HIV protease. Conversely, it also contributes to the depletion of CD4<sup>+</sup> T cells, a key feature of disease progression towards AIDS. The purpose of this review is to summarize the role of the CARD8 inflammasome in HIV pathogenesis, delving into its mechanisms of action and potential implications for the development of therapeutic strategies.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000488/pdfft?md5=db72195e8e4be00589a164a2210e8966&pid=1-s2.0-S2772892724000488-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death GLUD1 的去乙酰化通过抑制自噬性细胞死亡维持葡萄糖饥饿条件下肺腺癌细胞的存活

Cell insight Pub Date : 2024-07-16 DOI: 10.1016/j.cellin.2024.100186

Qifan Hu , Longhua Sun , Zhujun Cheng , Lei Wang , Xiaorui Wan , Jing Xu , Junyao Cheng , Zuorui Wang , Yi Yuan , Keru Wang , Tianyu Han

{"title":"Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death","authors":"Qifan Hu , Longhua Sun , Zhujun Cheng , Lei Wang , Xiaorui Wan , Jing Xu , Junyao Cheng , Zuorui Wang , Yi Yuan , Keru Wang , Tianyu Han","doi":"10.1016/j.cellin.2024.100186","DOIUrl":"10.1016/j.cellin.2024.100186","url":null,"abstract":"<div><p>Enhanced glutamine catabolism is one of the main metabolic features of cancer, providing energy and intermediate metabolites for cancer progression. However, the functions of glutamine catabolism in cancer under nutrient deprivation need to be further clarified. Here, we discovered that deacetylation of glutamate dehydrogenase 1 (GLUD1), one of the key enzymes in glutamine catabolism, maintains the survival of lung adenocarcinoma (LUAD) cells under glucose starvation by inhibiting autophagic cell death. We found that glucose starvation increased GLUD1 activity by reducing its acetylation on Lys84 and promoted its active hexamer formation. Besides, deacetylation of GLUD1 induced its cytoplasmic localization, where GLUD1 was ubiquitinated in K63-linkage by TRIM21, leading to the binding of GLUD1 with cytoplasmic glutaminase KGA. These two effects enhanced glutamine metabolism both in mitochondria and cytoplasm, increased the production of alpha-ketoglutarate (α-KG). Meanwhile, cytoplasmic GLUD1 also interacted with p62 and prevented its acetylation, leading to the inhibition of p62 body formation. All these effects blocked autophagic cell death of LUAD cells under glucose starvation. Taken together, our results reveal a novel function of GLUD1 under glucose deprivation in LUAD cells and provide new insights into the functions of glutamine catabolism during cancer progression.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000415/pdfft?md5=9b28cc74d459dd0b0adac81455611a6f&pid=1-s2.0-S2772892724000415-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The monkeypox virus-host interplays 猴痘病毒与宿主的相互作用

Cell insight Pub Date : 2024-07-14 DOI: 10.1016/j.cellin.2024.100185

Xue-Mei Yi , Ya-Li Lei , Mi Li , Li Zhong , Shu Li

引用次数: 0

Transcriptomic analysis of mouse TRAMP cell lines and tumors provide insights into shared pathways and therapeutic targets 小鼠 TRAMP 细胞系和肿瘤的转录组分析：洞察共享途径和治疗靶点

Cell insight Pub Date : 2024-07-14 DOI: 10.1016/j.cellin.2024.100184

Marxa L. Figueiredo , Sagar Utturkar , Shreya Kumar , Carlos Eduardo Fonseca-Alves

{"title":"Transcriptomic analysis of mouse TRAMP cell lines and tumors provide insights into shared pathways and therapeutic targets","authors":"Marxa L. Figueiredo , Sagar Utturkar , Shreya Kumar , Carlos Eduardo Fonseca-Alves","doi":"10.1016/j.cellin.2024.100184","DOIUrl":"10.1016/j.cellin.2024.100184","url":null,"abstract":"<div><p>The present study focused on comparing the gene expression profiles of different mouse models of prostate cancer, focusing on the TRAMP transgenic model and its derived cell lines and extending the comparisons to relevant genetically engineered mouse models and human prostate cancer datasets. Employing RNA sequencing, we examined different levels of prostate cancer aggressiveness from the original TRAMP cells to the TRAMP-C2 (TC2) derived cell line and extending to the aggressive TC2-Ras (TC2R) cells and tumors. TC2R acquire the ability to grow in bone tissue upon implantation, unlike the parental TC2 cells. Analysis identified upregulated genes in cell cycle regulation, immune response, and mitotic processes in TRAMP compared to wild-type tissues. TC2 cells exhibited unique gene profiles enriched in ECM organization and tissue development pathways, while TC2R cells showed increased cytokine signaling and motility genes, with decreased ECM and immune response pathways. <em>In vivo</em> TC2R models demonstrated enhanced ECM organization and receptor tyrosine kinase signaling in tumors, notably enriching immune processes and collagen degradation pathways in intratibial tumors. Comparative analysis among mouse and human datasets showed overlaps, particularly in pathways relating to mitotic cycle regulation, ECM organization, and immune interactions. A gene signature identified in TC2R tumors correlated with aggressive tumor behavior and poor survival in human datasets. Further immune cell landscape analysis of TC2R tumors revealed altered T cell subsets and macrophages, confirmed in single-cell RNA-seq from human samples. TC2R models thus hold significant promise in helping advance preclinical therapeutics, potentially contributing to improved prostate cancer patient outcomes.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000397/pdfft?md5=4524069e2dbfa3aa662ff78d8038cbac&pid=1-s2.0-S2772892724000397-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance ATR/Chk1相互作用的lncRNA调节DNA损伤反应，诱导乳腺癌化疗耐药性

Cell insight Pub Date : 2024-07-14 DOI: 10.1016/j.cellin.2024.100183

Rong Luo , Jiannan Wu , Xueman Chen , Yulan Liu , Dequan Liu , Erwei Song , Man-Li Luo

{"title":"ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance","authors":"Rong Luo , Jiannan Wu , Xueman Chen , Yulan Liu , Dequan Liu , Erwei Song , Man-Li Luo","doi":"10.1016/j.cellin.2024.100183","DOIUrl":"10.1016/j.cellin.2024.100183","url":null,"abstract":"<div><p>The ATR-Chk1 pathway is essential in cellular responses to DNA damage and replication stress, whereas the role of long noncoding RNAs (lncRNAs) in regulating this pathway remains largely unknown. In this study, we identify an ATR and Chk1 interacting lncRNA (ACIL, also known as LRRC75A-AS1 or SNHG29), which promotes the phosphorylation of Chk1 by ATR upon DNA damages. High ACIL levels are associated with chemoresistance to DNA damaging agents and poor outcome of breast cancer patients. ACIL knockdown sensitizes breast cancer cells to DNA damaging drugs <em>in vitro</em> and <em>in vivo</em>. ACIL protects cancer cells against DNA damages by inducing cell cycle arrest, stabilizing replication forks and inhibiting unscheduled origin firing, thereby guarding against replication catastrophe and contributing to DNA damage repair. These findings demonstrate a lncRNA-dependent mechanism of activating the ATR-Chk1 pathway and highlight the potential of utilizing ACIL as a predictive biomarker for chemotherapy sensitivity, as well as targeting ACIL to reverse chemoresistance in breast cancer.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 5","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000385/pdfft?md5=6755b14d725e10ac0eeb2f6f35905bc8&pid=1-s2.0-S2772892724000385-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141695249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0