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Cell insight Pub Date : 2024-10-01 DOI: 10.1016/S2772-8927(24)00057-9

引用次数: 0

Spontaneous and environment induced genomic alterations in yeast model 酵母模型中自发和环境诱导的基因组变化

Cell insight Pub Date : 2024-09-26 DOI: 10.1016/j.cellin.2024.100209

Ke-Jing Li , Lei Qi , Ying-Xuan Zhu , Min He , Qian Xiang , Dao-Qiong Zheng

{"title":"Spontaneous and environment induced genomic alterations in yeast model","authors":"Ke-Jing Li , Lei Qi , Ying-Xuan Zhu , Min He , Qian Xiang , Dao-Qiong Zheng","doi":"10.1016/j.cellin.2024.100209","DOIUrl":"10.1016/j.cellin.2024.100209","url":null,"abstract":"<div><div>While genomic alterations are fundamental to biological evolution, enabling adaptation and diversity, they can also result in detrimental outcomes, such as the development of genetic diseases including cancer. The budding yeast <em>Saccharomyces cerevisiae</em> serves as an exemplary model for investigating the mechanisms behind various genomic alterations, including point mutations, chromosomal rearrangements, and whole-chromosome aneuploidy. In this review, we highlight the application of genetic screening systems to assess the mutagenic effects of physical and chemical agents efficiently. Additionally, we discuss the utilization of high-throughput sequencing technologies to uncover comprehensive genomic alterations and rare genetic events. We provide a detailed summary of the features of genomic alterations and discuss the genetic mechanisms driving these changes under both spontaneous and stress-induced conditions. Given the high conservation of DNA replication and repair machinery across different organisms, the insights gained from studies on yeast offer valuable perspectives for understanding the delicate balance between genome plasticity and integrity in other species.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705407","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

Modeling respiratory tract diseases for clinical translation employing conditionally reprogrammed cells 利用条件重编程细胞建立呼吸道疾病模型，促进临床转化

Cell insight Pub Date : 2024-09-18 DOI: 10.1016/j.cellin.2024.100201

Danyal Daneshdoust , Kai He , Qi-En Wang , Jenny Li , Xuefeng Liu

{"title":"Modeling respiratory tract diseases for clinical translation employing conditionally reprogrammed cells","authors":"Danyal Daneshdoust , Kai He , Qi-En Wang , Jenny Li , Xuefeng Liu","doi":"10.1016/j.cellin.2024.100201","DOIUrl":"10.1016/j.cellin.2024.100201","url":null,"abstract":"<div><div>Preclinical models serve as indispensable tools in translational medicine. Specifically, patient-derived models such as patient-derived xenografts (PDX), induced pluripotent stem cells (iPSC), organoids, and recently developed technique of conditional reprogramming (CR) have been employed to reflect the host characteristics of diseases. CR technology involves co-culturing epithelial cells with irradiated Swiss-3T3-J2 mouse fibroblasts (feeder cells) in the presence of a Rho kinase (ROCK) inhibitor, Y-27632. CR technique facilitates the rapid conversion of both normal and malignant cells into a “reprogrammed stem-like” state, marked by robust in vitro proliferation. This is achieved without reliance on exogenous gene expression or viral transfection, while maintaining the genetic profile of the parental cells. So far, CR technology has been used to study biology of diseases, targeted therapies (precision medicine), regenerative medicine, and noninvasive diagnosis and surveillance. Respiratory diseases, ranking as the third leading cause of global mortality, pose a significant burden to healthcare systems worldwide. Given the substantial mortality and morbidity rates of respiratory diseases, efficient and rapid preclinical models are imperative to accurately recapitulate the diverse spectrum of respiratory conditions. In this article, we discuss the applications and future potential of CR technology in modeling various respiratory tract diseases, including lung cancer, respiratory viral infections (such as influenza and Covid-19 and etc.), asthma, cystic fibrosis, respiratory papillomatosis, and upper aerodigestive track tumors. Furthermore, we discuss the potential utility of CR in personalized medicine, regenerative medicine, and clinical translation.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 6","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000567/pdfft?md5=750759748ba4907ad4ed0e781caf4cc8&pid=1-s2.0-S2772892724000567-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314832","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 role of SUMOylation in biomolecular condensate dynamics and protein localization SUMOylation 在生物分子凝聚动态和蛋白质定位中的作用

Cell insight Pub Date : 2024-09-10 DOI: 10.1016/j.cellin.2024.100199

Emily Gutierrez-Morton, Yanchang Wang

{"title":"The role of SUMOylation in biomolecular condensate dynamics and protein localization","authors":"Emily Gutierrez-Morton, Yanchang Wang","doi":"10.1016/j.cellin.2024.100199","DOIUrl":"10.1016/j.cellin.2024.100199","url":null,"abstract":"<div><div>As a type of protein post-translational modification, SUMOylation is the process that attaches a small ubiquitin-like modifier (SUMO) to lysine residues of protein substrates. Not only do SUMO and ubiquitin exhibit structure similarity, but the enzymatic cascades for SUMOylation and ubiquitination are also similar. It is well established that protein ubiquitination triggers proteasomal degradation, but the function of SUMOylation remains poorly understood compared to ubiquitination. Recent studies reveal the role of SUMOylation in regulating protein localization, stability, and interaction networks. SUMO can be covalently attached to substrates either as an individual monomer (monoSUMOylation) or as a polymeric SUMO chain (polySUMOylation). Strikingly, mono- and polySUMOylation likely play distinct roles in protein subcellular localization and the assembly/disassembly of biomolecular condensates, which are membraneless cellular compartments with concentrated biomolecules. In this review, we summarize the recent advances in the understanding of the function and regulation of SUMOylation, which could reveal potential therapeutic targets in disease pathogenesis.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 6","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324172","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

Hypoxic reactivation of Kaposi's sarcoma associated herpesvirus 卡波西肉瘤相关疱疹病毒的缺氧再活化

Cell insight Pub Date : 2024-09-07 DOI: 10.1016/j.cellin.2024.100200

Rajnish Kumar Singh, Atharva S. Torne, Erle S. Robertson

{"title":"Hypoxic reactivation of Kaposi's sarcoma associated herpesvirus","authors":"Rajnish Kumar Singh, Atharva S. Torne, Erle S. Robertson","doi":"10.1016/j.cellin.2024.100200","DOIUrl":"10.1016/j.cellin.2024.100200","url":null,"abstract":"<div><div>Hypoxic reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) refers to the phenomenon under low oxygen where the virus goes from latent to lytic replication. Typically, healthy cells generally cease cell division and DNA replication under hypoxic conditions due to limited resources, and the presence of physiological inhibitors. This restricted replication under hypoxic conditions is considered an employed strategy of the cell to minimize energy consumption. However, cancerous cells continuously replicate and divide in hypoxic conditions by reprogramming several aspects of their cell physiology, including but not limited to metabolism, cell cycle, DNA replication, transcription, translation, and the epigenome. KSHV infection, similar to cancerous cells, is known to bypass hypoxia-induced restrictions and undergo reactivation to produce progeny viruses. In previous studies we have mapped several aspects of cell physiology that are manipulated by KSHV through its latent antigens during hypoxic conditions, which allows for a permissive environment for its replication. We discuss the major strategies utilized by KSHV to bypass hypoxia-induced repression. We also describe the KSHV-encoded antigens responsible for modulating these cellular processes important for successful viral replication and persistence in hypoxia.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 6","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319505","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

Insights into mosquito-borne arbovirus receptors 对蚊媒虫媒病毒受体的认识

Cell insight Pub Date : 2024-08-24 DOI: 10.1016/j.cellin.2024.100196

Jianying Liu , Yixin Quan , Hua Tong , Yibin Zhu , Xiaolu Shi , Yang Liu , Gong Cheng

{"title":"Insights into mosquito-borne arbovirus receptors","authors":"Jianying Liu , Yixin Quan , Hua Tong , Yibin Zhu , Xiaolu Shi , Yang Liu , Gong Cheng","doi":"10.1016/j.cellin.2024.100196","DOIUrl":"10.1016/j.cellin.2024.100196","url":null,"abstract":"<div><div>The increasing global prevalence of mosquito-borne viruses has emerged as a significant threat to human health and life. Identifying receptors for these viruses is crucial for improving our knowledge of viral pathogenesis and developing effective antiviral strategies. The widespread application of CRISPR-Cas9 screening have led to the discovery of many mosquito-borne virus receptors. The revealed structures of virus-receptor complexes also provide important information for understanding their interaction mechanisms. This review provides a comprehensive summary of both conventional and novel approaches for identifying new viral receptors and the putative entry factors of the most prevalent mosquito-borne viruses within the <em>Flaviviridae</em>, <em>Togaviridae</em>, and <em>Bunyavirales</em>. At the same time, we emphasize the common receptors utilized by these viruses for entry into both vertebrate hosts and mosquito vectors. We discuss promising avenues for developing anti-mosquito-borne viral strategies that target these receptors. Notably, targeting universal receptors of specific mosquito-borne viruses in both vertebrates and mosquitoes offers dual benefits for disease prevention. Additionally, the widespread use of AI-based machine learning and protein structure prediction will accelerate the identification of new viral receptors and provide new avenues for antiviral drug discovery.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 6","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772892724000518/pdfft?md5=b58af911ce662736b3c07a46c56b3b91&pid=1-s2.0-S2772892724000518-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314994","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

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