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A novel nuclear trafficking module regulates the nucleocytoplasmic localization of the rabies virus interferon antagonist, P protein.
Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L; Blondel, Danielle; Jans, David A; Moseley, Gregory W.
Afiliação
  • Oksayan S; Viral Immune Evasion and Pathogenicity Laboratory, Monash University, 3800 Victoria, Australia.
J Biol Chem ; 287(33): 28112-21, 2012 Aug 10.
Article em En | MEDLINE | ID: mdl-22700958
ABSTRACT
Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1-P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3-P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Raiva / Vírus da Raiva / Núcleo Celular / Sinais de Localização Nuclear / Citoplasma / Sinais de Exportação Nuclear Limite: Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Raiva / Vírus da Raiva / Núcleo Celular / Sinais de Localização Nuclear / Citoplasma / Sinais de Exportação Nuclear Limite: Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article