ArticlePLoS pathogens2013
Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections.Nature communications · 2023Article
- PLP2 Could Be a Prognostic Biomarker and Potential Treatment Target in Glioblastoma Multiforme.Pharmacogenomics and personalized medicine · 2023Article
- Genomic changes in Kaposi Sarcoma-associated Herpesvirus and their clinical correlates.PLoS pathogens · 2022Article
- CRISPR Tackles Emerging Viral Pathogens.Viruses · 2021Review
- Quantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.Cell reports · 2020Article
- Interferon-Responsive Genes Are Targeted during the Establishment of Human Cytomegalovirus Latency.mBio · 2019Article
- Exploring the tissue tropism of pseudorabies virus based on miRNA level analysis.BMC microbiology · 2019Article
- Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist.Cell reports · 2019Article
- MHC class II fine tuning by ubiquitination: lesson from MARCHs.Immunogenetics · 2019Review
- Identification of a Five-Gene Signature and Establishment of a Prognostic Nomogram to Predict Progression-Free Interval of Papillary Thyroid Carcinoma.Frontiers in endocrinology · 2019Article
- MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.EMBO reports · 2018Article
- Large-Scale Arrayed Analysis of Protein Degradation Reveals Cellular Targets for HIV-1 Vpu.Cell reports · 2018Article
- A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells.Cell reports · 2017Article
- Article
- A Genetic Screen Identifies a Critical Role for the WDR81-WDR91 Complex in the Trafficking and Degradation of Tetherin.Traffic (Copenhagen, Denmark) · 2016Article
- Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells.Journal of virology · 2016Article
- The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II.Journal of virology · 2016Article
- Hunting Viral Receptors Using Haploid Cells.Annual review of virology · 2015Review
- GENE SILENCING. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells.Science (New York, N.Y.) · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2), a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.