ArticlemBio2020
Nonproteolytic K29-Linked Ubiquitination of the PB2 Replication Protein of Influenza A Viruses by Proviral Cullin 4-Based E3 Ligases.
Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Cereblon promotes influenza A virus replication through AMPK ubiquitination.Biochemistry and biophysics reports · 2026Article
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- Ubiquitin-Dependent Regulation of Influenza A Virus Polymerase and vRNP Function: Mechanisms and Therapeutic Opportunities.Microorganisms · 2026Review
- The roles of post-translational modifications in the pathogenesis of RNA viruses: allies or adversaries?Frontiers in microbiology · 2026Review
- Post-translational modification networks as master regulators of influenza virus replication, host adaptation, and immune evasion.Frontiers in immunology · 2026Review
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- K29-Linked Ubiquitination of Transcription Regulators Controls Cell Proliferation in the Unfolded Protein Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- TRIM45 restricts influenza virus infection through modulating the chaperone-mediated autophagic degradation of viral PB2 protein.PLoS pathogens · 2025Article
- RNF20 dual regulation of MDA5 signaling to maintain immune homeostasis in chickens.Journal of virology · 2025Article
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Profiling Cullin4-E3 Ligases Interactomes and Their Rewiring in Influenza A Virus Infection.Molecular & cellular proteomics : MCP · 2024Article
- Ubiquitination of NS1 Confers Differential Adaptation of Zika Virus in Mammalian Hosts and Mosquito Vectors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- TRIM56 restricts Coxsackievirus B infection by mediating the ubiquitination of viral RNA-dependent RNA polymerase 3D.PLoS pathogens · 2024Article
- AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase.Virologica Sinica · 2024Article
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Role of protein Post-translational modifications in enterovirus infection.Frontiers in microbiology · 2024Review
- Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.Developmental cell · 2023Article
- USP39-mediated deubiquitination of Cyclin B1 promotes tumor cell proliferation and glioma progression.Translational oncology · 2023Article
- Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5'-termini of RNA and polymerase function.Scientific reports · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multifunctional nature of viral proteins is essentially driven by posttranslational modifications (PTMs) and is key for the successful outcome of infection. For influenza A viruses (IAVs), a composite pattern of PTMs regulates the activity of viral proteins. However, almost none are known that target the PB2 replication protein, except for inducing its degradation. We show here that PB2 undergoes a nonproteolytic ubiquitination during infection. We identified E3 ubiquitin ligases catalyzing this ubiquitination as two multicomponent RING-E3 ligases based on cullin 4 (CRL4s), which are both contributing to the levels of ubiquitinated forms of PB2 in infected cells. The CRL4 E3 ligase activity is required for the normal progression of the viral cycle and for maximal virion production, indicating that the CRL4s mediate a ubiquitin signaling that promotes infection. The CRL4s are recruiting PB2 through an unconventional bimodal interaction with both the DDB1 adaptor and DCAF substrate receptors. While able to bind to PB2 when engaged in the viral polymerase complex, the CRL4 factors do not alter transcription and replication of the viral segments during infection. CRL4 ligases catalyze different patterns of lysine ubiquitination on PB2. Recombinant viruses mutated in the targeted lysines showed attenuated viral production, suggesting that CRL4-mediated ubiquitination of PB2 contributes to IAV infection. We identified K29-linked ubiquitin chains as main components of the nonproteolytic PB2 ubiquitination mediated by the CRL4s, providing the first example of the role of this atypical ubiquitin linkage in the regulation of a viral infection.
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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.