TY - JOUR
T1 - The 37-amino-acid interdomain of dengue virus NS5 protein contains a functional NLS and inhibitory CK2 site
AU - Forwood, Jade K.
AU - Brooks, Andrew
AU - Briggs, Lyndall J.
AU - Xiao, Chong Yun
AU - Jans, David A.
AU - Vasudevan, Subhash G.
PY - 1999/4/21
Y1 - 1999/4/21
N2 - 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.
AB - 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.
KW - Bipartite nuclear localization sequence
KW - Dengue virus
KW - Importin subunits
KW - Protein kinase CK2-phosphorylation
KW - RNA dependent RNA polymerase
UR - http://www.scopus.com/inward/record.url?scp=0033590941&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.0370
DO - 10.1006/bbrc.1999.0370
M3 - Article
C2 - 10208852
AN - SCOPUS:0033590941
SN - 0006-291X
VL - 257
SP - 731
EP - 737
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
