Antiviral activity of a purine synthesis enzyme reveals a key role of deamidation in regulating protein nuclear import
Year: 2019
Type: article
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.
Source: Science Advances
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G2274692811, Exploring roles of protein deamidation in oral inflammation, The role of PHD12 in epigenetic control of cranial neural crest EMT, KSHV Persistence and Pathogenesis, Targeting an immune kinase to purge KSHV latent infection, NFAT activation in kGPCR tumorigenesis, G5169408845, Regulated MAVS-mediated signaling in KSHV lytic replication, Harnessing the therapeutic potential of neural crest cells by manipulating the primary cilium, IRF-1: a brake to limit gammaherpesvirus infection and pathogenesis, G7919806687, G8235091528
OpenAlex ID: W2979457612