Cell insightPub Date : 2024-10-11DOI: 10.1016/j.cellin.2024.100212
Chen Zhao , Liang Wang , Junbao Wang, Kuan Tian, Xiaojiao Hua, Fangyu Wang, Yan Zhou
{"title":"Transcripts derived from the neocortical enhancer of Ctnnb1 promote the enhancer-promoter interaction and maintain Ctnnb1 transcription","authors":"Chen Zhao , Liang Wang , Junbao Wang, Kuan Tian, Xiaojiao Hua, Fangyu Wang, Yan Zhou","doi":"10.1016/j.cellin.2024.100212","DOIUrl":"10.1016/j.cellin.2024.100212","url":null,"abstract":"","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100212"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651970","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}
Cell insightPub Date : 2024-10-11DOI: 10.1016/j.cellin.2024.100210
Yong Wang , Xinping Liu , Zheng Liu , Shasha Hua , Kai Jiang
{"title":"APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs","authors":"Yong Wang , Xinping Liu , Zheng Liu , Shasha Hua , Kai Jiang","doi":"10.1016/j.cellin.2024.100210","DOIUrl":"10.1016/j.cellin.2024.100210","url":null,"abstract":"<div><div>Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction. In addition, APC counteracts the major MT-stabilizer CLASPs at MT plus ends and promotes directional cell migration via modulating cell adhesion force. Reconstitution experiments demonstrate that APC potentiates KIF2A-induced MT catastrophes and antagonizes the stabilizing effect of CLASP2 <em>in vitro</em>. In summary, APC functions as a positive regulator of MT-destabilizer and a negative regulator of MT-stabilizer to orchestrate MT dynamics.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704837","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}
Cell insightPub Date : 2024-10-10DOI: 10.1016/j.cellin.2024.100214
Katherine N. Degner , Jessica L. Bell , Sean D. Jones , Hyejung Won
{"title":"Just a SNP away: The future of in vivo massively parallel reporter assay","authors":"Katherine N. Degner , Jessica L. Bell , Sean D. Jones , Hyejung Won","doi":"10.1016/j.cellin.2024.100214","DOIUrl":"10.1016/j.cellin.2024.100214","url":null,"abstract":"<div><div>The human genome is largely noncoding, yet the field is still grasping to understand how noncoding variants impact transcription and contribute to disease etiology. The massively parallel reporter assay (MPRA) has been employed to characterize the function of noncoding variants at unprecedented scales, but its application has been largely limited by the <em>in vitro</em> context. The field will benefit from establishing a systemic platform to study noncoding variant function across multiple tissue types under physiologically relevant conditions. However, to date, MPRA has been applied to only a handful of <em>in vivo</em> conditions. Given the complexity of the central nervous system and its widespread interactions with all other organ systems, our understanding of neuropsychiatric disorder-associated noncoding variants would be greatly advanced by studying their functional impact in the intact brain. In this review, we discuss the importance, technical considerations, and future applications of implementing MPRA in the <em>in vivo</em> space with the focus on neuropsychiatric disorders.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100214"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651969","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}
Cell insightPub Date : 2024-10-09DOI: 10.1016/j.cellin.2024.100211
Qiu Pan , Xiao-Lian Zhang
{"title":"Roles of core fucosylation modification in immune system and diseases","authors":"Qiu Pan , Xiao-Lian Zhang","doi":"10.1016/j.cellin.2024.100211","DOIUrl":"10.1016/j.cellin.2024.100211","url":null,"abstract":"<div><div>Core fucosylation, catalyzed by α1,6-fucosyltransferase (FUT8), is an important <em>N-</em>glycosylation modification process that attaches a fucose residue via an α1,6-linkage to the core <em>N</em>-acetylglucosamine of <em>N</em>-glycans in mammals. Research over the past three decades has revealed the critical role of FUT8-mediated core fucosylation modification in various physiological and pathological processes, including cell growth, adhesion, receptor activation, antibody-dependent cellular cytotoxicity (ADCC), tumor metastasis and infections. This review discusses the immune system function involving FUT8 and the mechanisms by which core fucosylation regulates immunity and contributes to disease. A deeper understanding of these mechanisms can provide insights into cellular biology and suggest new therapeutic approaches and targets for related diseases.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651844","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}
Cell insightPub Date : 2024-09-26DOI: 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}
Cell insightPub Date : 2024-09-18DOI: 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}
Cell insightPub Date : 2024-09-10DOI: 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}
Cell insightPub Date : 2024-09-07DOI: 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}
Cell insightPub Date : 2024-08-24DOI: 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}