Cell insight最新文献_第9页

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Cell insight Pub Date : 2023-08-01 DOI: 10.1016/S2772-8927(23)00040-8

引用次数: 0

The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop CHCHD2/Sirt1共抑制因子参与g9a介导的RNase H1表达调控以控制R-loop

Cell insight Pub Date : 2023-08-01 DOI: 10.1016/j.cellin.2023.100112

Le Li , Yequn Wu , Kui Dai, Qing Wang, Shiqi Ye, Qipeng Shi, Zhenfei Chen, Yi-Chun Huang, Weiwei Zhao, Lijia Li

{"title":"The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop","authors":"Le Li , Yequn Wu , Kui Dai, Qing Wang, Shiqi Ye, Qipeng Shi, Zhenfei Chen, Yi-Chun Huang, Weiwei Zhao, Lijia Li","doi":"10.1016/j.cellin.2023.100112","DOIUrl":"10.1016/j.cellin.2023.100112","url":null,"abstract":"<div><p>R-loops are regulators of many cellular processes and are threats to genome integrity. Therefore, understanding the mechanisms underlying the regulation of R-loops is important. Inspired by the findings on RNase H1-mediated R-loop degradation or accumulation, we focused our interest on the regulation of RNase H1 expression. In the present study, we report that G9a positively regulates RNase H1 expression to boost R-loop degradation. CHCHD2 acts as a repressive transcription factor that inhibits the expression of RNase H1 to promote R-loop accumulation. Sirt1 interacts with CHCHD2 and deacetylates it, which functions as a corepressor that suppresses the expression of downstream target gene <em>RNase H1</em>. We also found that G9a methylated the promoter of <em>RNase H1</em>, inhibiting the binding of CHCHD2 and Sirt1. In contrast, when G9a was knocked down, recruitment of CHCHD2 and Sirt1 to the <em>RNase H1</em> promoter increased, which co-inhibited <em>RNase H1</em> transcription. Furthermore, knockdown of Sirt1 led to binding of G9a to the <em>RNase H1</em> promoter. In summary, we demonstrated that G9a regulates RNase H1 expression to maintain the steady-state balance of R-loops by suppressing the recruitment of CHCHD2/Sirt1 corepressors to the target gene promoter.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 4","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/e6/main.PMC10300302.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741479","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

Morphogenesis and functional organization of viral inclusion bodies 病毒包涵体的形态发生和功能组织。

Cell insight Pub Date : 2023-06-01 DOI: 10.1016/j.cellin.2023.100103

Zhifei Li , Miaomiao Zheng , Zhicheng He , Yali Qin , Mingzhou Chen

{"title":"Morphogenesis and functional organization of viral inclusion bodies","authors":"Zhifei Li , Miaomiao Zheng , Zhicheng He , Yali Qin , Mingzhou Chen","doi":"10.1016/j.cellin.2023.100103","DOIUrl":"10.1016/j.cellin.2023.100103","url":null,"abstract":"<div><p>Eukaryotic viruses are obligate intracellular parasites that rely on the host cell machinery to carry out their replication cycle. This complex process involves a series of steps, starting with virus entry, followed by genome replication, and ending with virion assembly and release. Negative strand RNA and some DNA viruses have evolved to alter the organization of the host cell interior to create a specialized environment for genome replication, known as IBs, which are precisely orchestrated to ensure efficient viral replication. The biogenesis of IBs requires the cooperation of both viral and host factors. These structures serve multiple functions during infection, including sequestering viral nucleic acids and proteins from innate immune responses, increasing the local concentration of viral and host factors, and spatially coordinating consecutive replication cycle steps. While ultrastructural and functional studies have improved our understanding of IBs, much remains to be learned about the precise mechanisms of IB formation and function. This review aims to summarize the current understanding of how IBs are formed, describe the morphology of these structures, and highlight the mechanism of their functions. Given that the formation of IBs involves complex interactions between the virus and the host cell, the role of both viral and cellular organelles in this process is also discussed.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 3","pages":"Article 100103"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/66/main.PMC10164783.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9479091","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

Cover 盖

Cell insight Pub Date : 2023-06-01 DOI: 10.1016/S2772-8927(23)00029-9

引用次数: 0

Molecular basis for protein histidine N1-specific methylation of the “His-x-His” motifs by METTL9 METTL9对蛋白质组氨酸n1特异性“His-x-His”基序甲基化的分子基础

Cell insight Pub Date : 2023-06-01 DOI: 10.1016/j.cellin.2023.100090

Wentao Zhao , Yang Zhou , Caiyi Li , Yucong Bi , Keyun Wang , Mingliang Ye , Haitao Li

{"title":"Molecular basis for protein histidine N1-specific methylation of the “His-x-His” motifs by METTL9","authors":"Wentao Zhao , Yang Zhou , Caiyi Li , Yucong Bi , Keyun Wang , Mingliang Ye , Haitao Li","doi":"10.1016/j.cellin.2023.100090","DOIUrl":"10.1016/j.cellin.2023.100090","url":null,"abstract":"<div><p>Histidine methylation serves as an intriguing strategy to introduce altered traits of target proteins, including metal ion chelation, histidine-based catalysis, molecular assembly, and translation regulation. As a newly identified histidine methyltransferase, METTL9 catalyzes N1-methylation of protein substrates containing the “His-x-His” motif (HxH, x denotes small side chain residue). Here our structural and biochemical studies revealed that METTL9 specifically methylates the second histidine of the “HxH” motif, while exploiting the first one as a recognition signature. We observed an intimate engagement between METTL9 and a pentapeptide motif, where the small “x” residue is embedded and confined within the substrate pocket. Upon complex formation, the N3 atom of histidine imidazole ring is stabilized by an aspartate residue such that the N1 atom is presented to S-adenosylmethionine for methylation. Moreover, METTL9 displayed a feature in preferred consecutive and “C-to-N” directional methylation of tandem “HxH” repeats that exist in many METTL9 substrates. Collectively, our work illustrates the molecular design of METTL9 in N1-specific methylation of the broadly existing “HxH” motifs, highlighting its importance in histidine methylation biology.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 3","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/45/main.PMC10308197.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9747066","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: 1

The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection 去泛素酶OTUD4抑制Paneth细胞中抗菌肽的表达，以支持肠道炎症和细菌感染。

Cell insight Pub Date : 2023-06-01 DOI: 10.1016/j.cellin.2023.100100

Keying Yu , Yu-Yao Guo , Tianzi Liuyu , Peng Wang , Zhi-Dong Zhang , Dandan Lin , Bo Zhong

{"title":"The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection","authors":"Keying Yu , Yu-Yao Guo , Tianzi Liuyu , Peng Wang , Zhi-Dong Zhang , Dandan Lin , Bo Zhong","doi":"10.1016/j.cellin.2023.100100","DOIUrl":"10.1016/j.cellin.2023.100100","url":null,"abstract":"<div><p>Dysfunction of the intestinal epithelial barrier causes microbial invasion that would lead to inflammation in the gut. Antimicrobial peptides (AMPs) are essential components of the intestinal epithelial barrier, while the regulatory mechanisms of AMPs expression are not fully characterized. Here, we report that the ovarian tumor family deubiquitinase 4 (OTUD4) in Paneth cells restricts the expression of AMPs and thereby promotes experimental colitis and bacterial infection. OTUD4 is upregulated in the inflamed mucosa of ulcerative colitis patients and in the colon of mice treated with dextran sulfate sodium salt (DSS). Knockout of OTUD4 promotes the expression of AMPs in intestinal organoids after stimulation with lipopolysaccharide (LPS) or peptidoglycan (PGN) and in the intestinal epithelial cells (IECs) of mice after DSS treatment or <em>Salmonella</em> typhimurium (<em>S</em>.t.) infection. Consistently, <em>Vil</em>-Cre;<em>Otud4</em><sup>fl/fl</sup> mice and <em>Def</em>-Cre;<em>Otud4</em><sup>fl/fl</sup> mice exhibit hyper-resistance to DSS-induced colitis and <em>S</em>.t. infection compared to <em>Otud4</em><sup>fl/fl</sup> mice. Mechanistically, knockout of OTUD4 results in hyper K63-linked ubiquitination of MyD88 and increases the activation of NF-κB and MAPKs to promote the expression of AMPs. These findings collectively highlight an indispensable role of OTUD4 in Paneth cells to modulate AMPs production and indicate OTUD4 as a potential target for gastrointestinal inflammation and bacterial infection.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 3","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490725","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

Origins of nervous tissue susceptibility to ferroptosis 神经组织对铁下垂易感性的起源

Cell insight Pub Date : 2023-06-01 DOI: 10.1016/j.cellin.2023.100091

Jessica Snyder, Zhihao Wu

引用次数: 0

Antiviral PROTACs: Opportunity borne with challenge 抗病毒PROTACs:机遇与挑战并存

Cell insight Pub Date : 2023-06-01 DOI: 10.1016/j.cellin.2023.100092

Jinsen Liang , Yihe Wu , Ke Lan , Chune Dong , Shuwen Wu , Shu Li , Hai-Bing Zhou

{"title":"Antiviral PROTACs: Opportunity borne with challenge","authors":"Jinsen Liang , Yihe Wu , Ke Lan , Chune Dong , Shuwen Wu , Shu Li , Hai-Bing Zhou","doi":"10.1016/j.cellin.2023.100092","DOIUrl":"10.1016/j.cellin.2023.100092","url":null,"abstract":"<div><p>Proteolysis targeting chimera (PROTAC) degradation of pathogenic proteins by hijacking of the ubiquitin-proteasome-system has become a promising strategy in drug design. The overwhelming advantages of PROTAC technology have ensured a rapid and wide usage, and multiple PROTACs have entered clinical trials. Several antiviral PROTACs have been developed with promising bioactivities against various pathogenic viruses. However, the number of reported antiviral PROTACs is far less than that of other diseases, e.g., cancers, immune disorders, and neurodegenerative diseases, possibly because of the common deficiencies of PROTAC technology (e.g., limited available ligands and poor membrane permeability) plus the complex mechanism involved and the high tendency of viral mutation during transmission and replication, which may challenge the successful development of effective antiviral PROTACs. This review highlights the important advances in this rapidly growing field and critical limitations encountered in developing antiviral PROTACs by analyzing the current status and representative examples of antiviral PROTACs and other PROTAC-like antiviral agents. We also summarize and analyze the general principles and strategies for antiviral PROTAC design and optimization with the intent of indicating the potential strategic directions for future progress.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 3","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/84/main.PMC10308200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9747065","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: 5

Advances in deciphering the interactions between viral proteins of influenza A virus and host cellular proteins 甲型流感病毒病毒蛋白与宿主细胞蛋白相互作用的研究进展。

Cell insight Pub Date : 2023-04-01 DOI: 10.1016/j.cellin.2023.100079

Li Jiang, Hualan Chen, Chengjun Li

{"title":"Advances in deciphering the interactions between viral proteins of influenza A virus and host cellular proteins","authors":"Li Jiang, Hualan Chen, Chengjun Li","doi":"10.1016/j.cellin.2023.100079","DOIUrl":"10.1016/j.cellin.2023.100079","url":null,"abstract":"<div><p>Influenza A virus (IAV) poses a severe threat to the health of animals and humans. The genome of IAV consists of eight single-stranded negative-sense RNA segments, encoding ten essential proteins as well as certain accessory proteins. In the process of virus replication, amino acid substitutions continuously accumulate, and genetic reassortment between virus strains readily occurs. Due to this high genetic variability, new viruses that threaten animal and human health can emerge at any time. Therefore, the study on IAV has always been a focus of veterinary medicine and public health. The replication, pathogenesis, and transmission of IAV involve intricate interplay between the virus and host. On one hand, the entire replication cycle of IAV relies on numerous proviral host proteins that effectively allow the virus to adapt to its host and support its replication. On the other hand, some host proteins play restricting roles at different stages of the viral replication cycle. The mechanisms of interaction between viral proteins and host cellular proteins are currently receiving particular interest in IAV research. In this review, we briefly summarize the current advances in our understanding of the mechanisms by which host proteins affect virus replication, pathogenesis, or transmission by interacting with viral proteins. Such information about the interplay between IAV and host proteins could provide insights into how IAV causes disease and spreads, and might help support the development of antiviral drugs or therapeutic approaches.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 2","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490714","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: 5

Inhibition of TRPP3 by calmodulin through Ca2+/calmodulin-dependent protein kinase II 钙调素通过Ca2+/钙调素依赖性蛋白激酶II抑制TRPP3

Cell insight Pub Date : 2023-04-01 DOI: 10.1016/j.cellin.2023.100088

Xiong Liu , Yifang Wang , Ziyi Weng , Qinyi Xu , Cefan Zhou , JingFeng Tang , Xing-Zhen Chen

引用次数: 0