ArticleThe Journal of biological chemistry2014
Role of protein phosphatase 1 in dephosphorylation of Ebola virus VP30 protein and its targeting for the inhibition of viral transcription.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 85 citations in OpenAlex.
- Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events.Nature communications · 2026Article
- Review
- To be or not to be phosphorylated: understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56.Emerging microbes & infections · 2025Article
- Conserved Filovirus Proteins as Targets of Broad-Spectrum Antivirals.bioRxiv : the preprint server for biology · 2025Article
- Article
- Hippo signaling pathway regulates Ebola virus transcription and egress.Nature communications · 2024Article
- CK1 and PP1 regulate Rift Valley fever virus genome replication through L protein phosphorylation.Antiviral research · 2024Article
- Molecular insights into the Ebola virus life cycle.Nature microbiology · 2024Review
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- Defining Distinct RNA-Protein Interactomes of SARS-CoV-2 Genomic and Subgenomic RNAs.Journal of proteome research · 2024Article
- Serine-arginine protein kinases and their targets in viral infection and their inhibition.Cellular and molecular life sciences : CMLS · 2023Review
- PP1, PP2A and PP2B Interplay in the Regulation of Sperm Motility: Lessons from Protein Phosphatase Inhibitors.International journal of molecular sciences · 2022Review
- Article
- Evidence for Viral mRNA Export from Ebola Virus Inclusion Bodies by the Nuclear RNA Export Factor NXF1.Journal of virology · 2022Article
- Ubiquitination of Ebola virus VP35 at lysine 309 regulates viral transcription and assembly.PLoS pathogens · 2022Article
- Functional interactomes of the Ebola virus polymerase identified by proximity proteomics in the context of viral replication.Cell reports · 2022Article
- Therapeutic Strategies against Ebola Virus Infection.Viruses · 2022Review
- Comparison of Intracellular Transcriptional Response of NHBE Cells to Infection with SARS-CoV-2 Washington and New York Strains.Frontiers in cellular and infection microbiology · 2022Article
- Structural and Functional Aspects of Ebola Virus Proteins.Pathogens (Basel, Switzerland) · 2021Review
- Non-canonical proline-tyrosine interactions with multiple host proteins regulate Ebola virus infection.The EMBO journal · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The filovirus Ebola (EBOV) causes the most severe hemorrhagic fever known. The EBOV RNA-dependent polymerase complex includes a filovirus-specific VP30, which is critical for the transcriptional but not replication activity of EBOV polymerase; to support transcription, VP30 must be in a dephosphorylated form. Here we show that EBOV VP30 is phosphorylated not only at the N-terminal serine clusters identified previously but also at the threonine residues at positions 143 and 146. We also show that host cell protein phosphatase 1 (PP1) controls VP30 dephosphorylation because expression of a PP1-binding peptide cdNIPP1 increased VP30 phosphorylation. Moreover, targeting PP1 mRNA by shRNA resulted in the overexpression of SIPP1, a cytoplasm-shuttling regulatory subunit of PP1, and increased EBOV transcription, suggesting that cytoplasmic accumulation of PP1 induces EBOV transcription. Furthermore, we developed a small molecule compound, 1E7-03, that targeted a non-catalytic site of PP1 and increased VP30 dephosphorylation. The compound inhibited the transcription but increased replication of the viral genome and completely suppressed replication of EBOV in cultured cells. Finally, mutations of Thr(143) and Thr(146) of VP30 significantly inhibited EBOV transcription and strongly induced VP30 phosphorylation in the N-terminal Ser residues 29-46, suggesting a novel mechanism of regulation of VP30 phosphorylation. Our findings suggest that targeting PP1 with small molecules is a feasible approach to achieve dysregulation of the EBOV polymerase activity. This novel approach may be used for the development of antivirals against EBOV and other filovirus species.
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