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DOI | 10.1073/pnas.2015794118 |
E3 ubiquitin ligase Mindbomb 1 facilitates nuclear delivery of adenovirus genomes | |
Sarbanes S.L.; Blomen V.A.; Lam E.; Heissel S.; Luna J.M.; Brummelkamp T.R.; Falck-Pedersen E.; Hoffmann H.H.; Rice C.M. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:1 |
英文摘要 | The journey from plasma membrane to nuclear pore is a critical step in the lifecycle of DNA viruses, many of which must successfully deposit their genomes into the nucleus for replication. Viral capsids navigate this vast distance through the coordinated hijacking of a number of cellular host factors, many of which remain unknown. We performed a gene-trap screen in haploid cells to identify host factors for adenovirus (AdV), a DNA virus that can cause severe respiratory illness in immune-compromised individuals. This work identified Mindbomb 1 (MIB1), an E3 ubiquitin ligase involved in neurodevelopment, as critical for AdV infectivity. In the absence of MIB1, we observed that viral capsids successfully traffic to the proximity of the nucleus but ultimately fail to deposit their genomes within. The capacity of MIB1 to promote AdV infection was dependent on its ubiquitination activity, suggesting that MIB1 may mediate proteasomal degradation of one or more negative regulators of AdV infection. Employing complementary proteomic approaches to characterize proteins proximal to MIB1 upon AdV infection and differentially ubiquitinated in the presence or absence of MIB1, we observed an intersection between MIB1 and ribonucleoproteins (RNPs) largely unexplored in mammalian cells. This work uncovers yet another way that viruses utilize host cell machinery for their own replication, highlighting a potential target for therapeutic interventions that counter AdV infection. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | Adenovirus; E3 ubiquitin ligase; Host factor; Mindbomb 1; Viral entry |
语种 | 英语 |
scopus关键词 | Mindbomb 1 ligase; proteasome; ribonucleoprotein; ubiquitin protein ligase E3; unclassified drug; Adenoviridae; Article; controlled study; enzyme activity; enzyme degradation; nonhuman; priority journal; protein expression; proteomics; ubiquitination; virus capsid; virus genome; virus replication; virus strain; wild type |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/181146 |
作者单位 | Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, United States; Oncode Institute, Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, 1066CX, Netherlands; Molecular Biology Graduate Program, Department of Microbiology and Immunology, Hearst Research Foundation, Weill Medical College of Cornell University, New York, NY 10021, United States; Proteomics Resource Center, The Rockefeller University, New York, NY 10065, United States; CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, A-1090, Austria; Cancer Genomics Center, Amsterdam, 1066CX, Netherlands |
推荐引用方式 GB/T 7714 | Sarbanes S.L.,Blomen V.A.,Lam E.,et al. E3 ubiquitin ligase Mindbomb 1 facilitates nuclear delivery of adenovirus genomes[J],2021,118(1). |
APA | Sarbanes S.L..,Blomen V.A..,Lam E..,Heissel S..,Luna J.M..,...&Rice C.M..(2021).E3 ubiquitin ligase Mindbomb 1 facilitates nuclear delivery of adenovirus genomes.Proceedings of the National Academy of Sciences of the United States of America,118(1). |
MLA | Sarbanes S.L.,et al."E3 ubiquitin ligase Mindbomb 1 facilitates nuclear delivery of adenovirus genomes".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021). |
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