Nucleocytoplasmic Distribution of Rabies Virus P-Protein Is Regulated by Phosphorylation Adjacent to C-Terminal Nuclear Import and Export Signals

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• 作者：Gregory W. Moseley ; Richard P. Filmer ; Michelle A. DeJesus ; David A. Jans
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：October 30, 2007
• 年：2007
• 卷：46
• 期：43
• 页码：12053 - 12061
• 全文大小：565K
• 年卷期：v.46,no.43(October 30, 2007)
• ISSN：1520-4995

文摘

Nucleocytoplasmic distribution of the rabies virus phosphoprotein is implicated in the evasionof cellular antiviral mechanisms by rabies virus and has been reported to depend on an N-terminal nuclearexport sequence and a C-terminal nuclear localization sequence. This paper identifies a second nuclearexport sequence that is located between key residues of the nuclear localization sequence in thephosphoprotein C-terminal domain. The C-terminal domain confers predominantly nuclear localizationin unstimulated transfected cells, indicating that the nuclear localization sequence is the dominant signalat steady state. However, protein kinase-C activation or mutagenesis to mimic protein kinase-Cphosphorylation at a site proximal to the C-terminal nuclear localization/export sequences shifts the targetingactivity of the C-terminal domain toward nuclear exclusion, indicating that the nuclear export sequencebecomes the dominant signal in activated cells. Mapping of these sequences within the three-dimensionalstructure of the C-terminal domain indicates that their activities may be coregulated by phosphorylationand/or conformational changes in the domain. The data are consistent with a model in which intimatepositioning of the nuclear localization sequence, export sequence, and phosphorylation site within a singledomain provides a switch mechanism to rapidly and efficiently balance the reciprocal import and exportsignals in response to cellular stimuli.