Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2006 Aug 15;10333:12417-22. doi: 10.1073/pnas.0605375103.
Show Gene links
Show Anatomy links
A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic transport.
Porter FW
,
Bochkov YA
,
Albee AJ
,
Wiese C
,
Palmenberg AC
.
???displayArticle.abstract???
Active nucleocytoplasmic transport of protein and RNA in eukaryotes depends on the Ran-GTPase system to regulate cargo-receptor interactions. Several viruses, including the RNA picornaviruses, encode factors that alter nuclear transport with the aim of suppressing synthesis of antiviral factors and promoting viral replication. Picornaviruses in the cardiovirus genus express a unique 67-aa Leader protein (L), known to alter the subcellular distribution of IFN regulatory proteins targeted to the nucleus. We report here that L binds directly to Ran and blocks nuclear export of new mRNAs. In Xenopus egg extracts, recombinant L also inhibits mitotic spindle assembly, a RanGTP function crucial to cell-cycle progression. We propose that L inhibits nucleocytoplasmic transport during infection by disrupting the RanGDP/GTP gradient. This inhibition triggers an efflux of nuclear proteins necessary for viral replication and causes IFN suppression. To our knowledge, L is the first viral picornaviral protein to interact directly with Ran and modulate the Ran-dependent nucleocytoplasmic pathway.
Adam,
Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.
1990, Pubmed,
Xenbase
Adam,
Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.
1990,
Pubmed
,
Xenbase
Aminev,
Encephalomyocarditis viral protein 2A localizes to nucleoli and inhibits cap-dependent mRNA translation.
2003,
Pubmed
Belov,
Bidirectional increase in permeability of nuclear envelope upon poliovirus infection and accompanying alterations of nuclear pores.
2004,
Pubmed
Bischoff,
RanGAP1 induces GTPase activity of nuclear Ras-related Ran.
1994,
Pubmed
Caudron,
Spatial coordination of spindle assembly by chromosome-mediated signaling gradients.
2005,
Pubmed
,
Xenbase
Dasso,
The Ran GTPase: theme and variations.
2002,
Pubmed
Delhaye,
The leader protein of Theiler's virus interferes with nucleocytoplasmic trafficking of cellular proteins.
2004,
Pubmed
Duke,
Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation.
1992,
Pubmed
Dvorak,
Leader protein of encephalomyocarditis virus binds zinc, is phosphorylated during viral infection, and affects the efficiency of genome translation.
2001,
Pubmed
Gruss,
Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity.
2001,
Pubmed
,
Xenbase
Gustin,
Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition.
2001,
Pubmed
Gustin,
Inhibition of nuclear import and alteration of nuclear pore complex composition by rhinovirus.
2002,
Pubmed
Görlich,
Transport between the cell nucleus and the cytoplasm.
1999,
Pubmed
Görlich,
Identification of different roles for RanGDP and RanGTP in nuclear protein import.
1996,
Pubmed
,
Xenbase
Hahn,
Encephalomyocarditis viruses with short poly(C) tracts are more virulent than their mengovirus counterparts.
1995,
Pubmed
Kalab,
Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts.
2002,
Pubmed
,
Xenbase
Lidsky,
Nucleocytoplasmic traffic disorder induced by cardioviruses.
2006,
Pubmed
Lounsbury,
Mutations within the Ran/TC4 GTPase. Effects on regulatory factor interactions and subcellular localization.
1996,
Pubmed
Macara,
Transport into and out of the nucleus.
2001,
Pubmed
Molla,
Cell-free, de novo synthesis of poliovirus.
1991,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nachury,
Importin beta is a mitotic target of the small GTPase Ran in spindle assembly.
2001,
Pubmed
,
Xenbase
O'Brien,
The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly.
2005,
Pubmed
,
Xenbase
Rose,
A new cationic liposome reagent mediating nearly quantitative transfection of animal cells.
1991,
Pubmed
Rueckert,
Preparation and characterization of encephalomyocarditis (EMC) virus.
1981,
Pubmed
Seewald,
Biochemical characterization of the Ran-RanBP1-RanGAP system: are RanBP proteins and the acidic tail of RanGAP required for the Ran-RanGAP GTPase reaction?
2003,
Pubmed
Sen,
Interferon-induced antiviral actions and their regulation.
1993,
Pubmed
Stewart,
Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import.
2001,
Pubmed
Weis,
The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import.
1996,
Pubmed
Wiese,
Role of importin-beta in coupling Ran to downstream targets in microtubule assembly.
2001,
Pubmed
,
Xenbase
Wilde,
Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities.
2001,
Pubmed
,
Xenbase
Wilde,
Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran.
1999,
Pubmed
,
Xenbase
Zoll,
Mengovirus leader is involved in the inhibition of host cell protein synthesis.
1996,
Pubmed
Zoll,
The mengovirus leader protein suppresses alpha/beta interferon production by inhibition of the iron/ferritin-mediated activation of NF-kappa B.
2002,
Pubmed
