West Nile virus capsid protein interaction with importin and HDM2 protein is regulated by protein kinase C-mediated phosphorylation.
Microbes Infect
; 12(8-9): 615-25, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20417716
ABSTRACT
West Nile virus (WNV) capsid (C) protein was shown to enter the nucleus via importin-mediated pathway and induce apoptosis although the precise regulatory mechanisms for such events have remained elusive. In this study, it was shown that WNV C protein was phosphorylated by protein kinase C (PKC). PKC-mediated phosphorylation influenced nuclear trafficking of C protein by modulating the efficiency of C protein-importin-alpha binding. Combination of bio-informatics, site-directed mutagenesis, co-immunoprecipitation, immuno-fluorescence and mammalian two-hybrid analyses showed that phosphorylation at amino acid residues residing near (Ser83) or within (Ser99 and Thr100) the bipartite nuclear localization motif of WNV C protein was essential for efficient interaction between C protein and importin-alpha. In addition, phosphorylation of WNV C protein by PKC was shown to enhance its binding to HDM2 and could subsequently induce p53-dependent apoptosis. Collectively, this study highlighted that phosphorylation is an important post-translational modification required to execute the functions of C protein.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus do Nilo Ocidental
/
Proteína Quinase C
/
Carioferinas
/
Proteínas do Capsídeo
/
Proteínas Proto-Oncogênicas c-mdm2
Limite:
Animals
Idioma:
En
Revista:
Microbes Infect
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
MICROBIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Singapura