The 37-amino-acid interdomain of dengue virus NS5 protein contains a functional NLS and inhibitory CK2 site

Jade K. Forwood, Andrew Brooks, Lyndall J. Briggs, Chong Yun Xiao, David A. Jans, Subhash G. Vasudevan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The dengue virus NS5 RNA-dependent RNA polymerase has been detected in the nucleus of virus-infected mammalian cells. We demonstrate here for the first time using in vitro and in vivo assay systems that the 37-amino-acid linker interdomain of NS5 (residues 369 to 405) contains a nuclear localization sequence (NLS) which is capable of targeting b-galactosidase to the nucleus. Further, we show that the linker is recognized by subunits of the NLS-binding importin complex with an affinity similar to that of the bipartite NLS of the retinoblastoma protein and, in analogous fashion to proteins such as the SV40 large tumor antigen, contains a functional protein kinase CK2 phosphorylation site (threonine 395). Interestingly, this site appears to inhibit NS5 nuclear targeting, probably through a cytoplasmic retention mechanism. The linker may have an important role in targeting NS5 to the nucleus in a regulated manner during the dengue virus infectious cycle.

Original languageEnglish
Pages (from-to)731-737
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume257
Issue number3
DOIs
Publication statusPublished - 21 Apr 1999
Externally publishedYes

Keywords

  • Bipartite nuclear localization sequence
  • Dengue virus
  • Importin subunits
  • Protein kinase CK2-phosphorylation
  • RNA dependent RNA polymerase

Cite this

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title = "The 37-amino-acid interdomain of dengue virus NS5 protein contains a functional NLS and inhibitory CK2 site",
abstract = "The dengue virus NS5 RNA-dependent RNA polymerase has been detected in the nucleus of virus-infected mammalian cells. We demonstrate here for the first time using in vitro and in vivo assay systems that the 37-amino-acid linker interdomain of NS5 (residues 369 to 405) contains a nuclear localization sequence (NLS) which is capable of targeting b-galactosidase to the nucleus. Further, we show that the linker is recognized by subunits of the NLS-binding importin complex with an affinity similar to that of the bipartite NLS of the retinoblastoma protein and, in analogous fashion to proteins such as the SV40 large tumor antigen, contains a functional protein kinase CK2 phosphorylation site (threonine 395). Interestingly, this site appears to inhibit NS5 nuclear targeting, probably through a cytoplasmic retention mechanism. The linker may have an important role in targeting NS5 to the nucleus in a regulated manner during the dengue virus infectious cycle.",
keywords = "Bipartite nuclear localization sequence, Dengue virus, Importin subunits, Protein kinase CK2-phosphorylation, RNA dependent RNA polymerase",
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The 37-amino-acid interdomain of dengue virus NS5 protein contains a functional NLS and inhibitory CK2 site. / Forwood, Jade K.; Brooks, Andrew; Briggs, Lyndall J.; Xiao, Chong Yun; Jans, David A.; Vasudevan, Subhash G.

In: Biochemical and Biophysical Research Communications, Vol. 257, No. 3, 21.04.1999, p. 731-737.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Forwood, Jade K.

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