ArticleScience advances2019
Antiviral activity of a purine synthesis enzyme reveals a key role of deamidation in regulating protein nuclear import.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- m5C RNA methylation is dysregulated by oncogenic herpesviruses via c-Myc signaling to counteract host antiviral factors.Nucleic acids research · 2026Article
- H1N76/77 deamidation facilitates chromatin remodelling and genome stability during DNA damage repair.Clinical and translational medicine · 2025Article
- Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection.PLoS pathogens · 2025Article
- Article
- Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation.Virologica Sinica · 2025Article
- Article
- Pyrimidine synthesis enzyme CTP synthetase 1 suppresses antiviral interferon induction by deamidating IRF3.Immunity · 2025Article
- Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins.Nature metabolism · 2024Article
- Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway.Science China. Life sciences · 2024Article
- Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production.PLoS pathogens · 2024Article
- Modulation of nucleotide metabolism by picornaviruses.PLoS pathogens · 2024Article
- Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus.Nature communications · 2024Article
- Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.PLoS pathogens · 2024Article
- Review
- The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection.bioRxiv : the preprint server for biology · 2023Article
- An unnatural enzyme with endonuclease activity towards small non-coding RNAs.Nature communications · 2023Article
- An aquatic virus exploits the IL6-STAT3-HSP90 signaling axis to promote viral entry.PLoS pathogens · 2023Article
- Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection.PLoS pathogens · 2022Article
- The regulation of KSHV lytic reactivation by viral and cellular factors.Current opinion in virology · 2022Review
- Viral pseudoenzymes in infection and immunity.The FEBS journal · 2020Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Protein nuclear translocation is highly regulated and crucial for diverse biological processes. However, our understanding concerning protein nuclear import is incomplete. Here we report that a cellular purine synthesis enzyme inhibits protein nuclear import via deamidation. Employing human Kaposi's sarcoma-associated herpesvirus (KSHV) to probe the role of protein deamidation, we identified a purine synthesis enzyme, phosphoribosylformylglycinamidine synthetase (PFAS) that inhibits KSHV transcriptional activation. PFAS deamidates the replication transactivator (RTA), a transcription factor crucial for KSHV lytic replication. Mechanistically, deamidation of two asparagines flanking a positively charged nuclear localization signal impaired the binding of RTA to an importin β subunit, thus diminishing RTA nuclear localization and transcriptional activation. Finally, RTA proteins of all gamma herpesviruses appear to be regulated by PFAS-mediated deamidation. These findings uncover an unexpected function of a metabolic enzyme in restricting viral replication and a key role of deamidation in regulating protein nuclear import.
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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.