Antiviral activity of a purine synthesis enzyme reveals a key role of deamidation in regulating protein nuclear import.
Sci Adv
; 5(10): eaaw7373, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31633017
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 ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transativadores
/
Proteínas Imediatamente Precoces
/
Herpesvirus Humano 8
/
Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos