PMID- 18003734
OWN - NLM
STAT- MEDLINE
DCOM- 20080124
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 82
IP  - 2
DP  - 2008 Jan
TI  - Characterization of the human herpesvirus 6 U69 gene product and identification 
      of its nuclear localization signal.
PG  - 710-8
AB  - To elucidate the function of the U69 protein kinase of human herpesvirus 6 
      (HHV-6) in vivo, we first analyzed its subcellular localization in HHV-6-infected 
      Molt 3 cells by using polyclonal antibodies against the U69 protein. 
      Immunofluorescence studies showed that the U69 signal localized to the nucleus in 
      a mesh-like pattern in both HHV-6-infected and HHV6-transfected cells. A computer 
      program predicted two overlapping classic nuclear localization signals (NLSs) in 
      the N-terminal region of the protein; this NLS motif is highly conserved in the 
      N-terminal region of most of the herpesvirus protein kinases examined to date. An 
      N-terminal deletion mutant form of the protein failed to enter the nucleus, 
      whereas a fusion protein of green fluorescent protein (GFP) and/or glutathione 
      S-transferase (GST) and the U69 N-terminal region was transported into the 
      nucleus, demonstrating that the predicted N-terminal NLSs of the protein actually 
      function as NLSs. The nuclear transport of the GST-GFP fusion protein containing 
      the N-terminal NLS of U69 was inhibited by wheat germ agglutinin and by the Q69L 
      Ran-GTP mutant, indicating that the U69 protein is transported into the nucleus 
      from the cytoplasm via classic nuclear transport machinery. A cell-free import 
      assay showed that the nuclear transport of the U69 protein was mediated by 
      importin alpha/beta in conjunction with the small GTPase Ran. When the import 
      assay was performed with a low concentration of each importin-alpha subtype, 
      NPI2/importin-alpha7 elicited more efficient transport activity than did 
      Rch1/importin-alpha1 or Qip1/importin-alpha3. These results suggest a 
      relationship between the localization of NPI2/importin-alpha7 and the cell 
      tropism of HHV-6.
FAU - Isegawa, Yuji
AU  - Isegawa Y
AD  - Department of Infectious Disease Control, G-5, Graduate School of Medicine, Osaka 
      University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. 
      isegawa@bact.med.osaka-u.ac.jp
FAU - Miyamoto, Yoichi
AU  - Miyamoto Y
FAU - Yasuda, Yoshinari
AU  - Yasuda Y
FAU - Semi, Katsunori
AU  - Semi K
FAU - Tsujimura, Kenji
AU  - Tsujimura K
FAU - Fukunaga, Rikiro
AU  - Fukunaga R
FAU - Ohshima, Atsushi
AU  - Ohshima A
FAU - Horiguchi, Yasuhiro
AU  - Horiguchi Y
FAU - Yoneda, Yoshihiro
AU  - Yoneda Y
FAU - Sugimoto, Nakaba
AU  - Sugimoto N
LA  - eng
PT  - Journal Article
DEP - 20071114
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (pU69 kinase, human herpesvirus 6)
SB  - IM
MH  - Active Transport, Cell Nucleus/physiology
MH  - Cell Line
MH  - Cell Nucleus/chemistry
MH  - Cells, Cultured
MH  - Glutathione Transferase/analysis/genetics
MH  - Green Fluorescent Proteins/analysis/genetics
MH  - Herpesvirus 6, Human/genetics/*physiology
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - *Nuclear Localization Signals
MH  - Phosphotransferases (Alcohol Group Acceptor)/*analysis/genetics/*physiology
MH  - Recombinant Fusion Proteins/analysis/genetics
MH  - Sequence Deletion
PMC - PMC2224601
EDAT- 2007/11/16 09:00
MHDA- 2008/01/25 09:00
PMCR- 2008/05/01
CRDT- 2007/11/16 09:00
PHST- 2007/11/16 09:00 [pubmed]
PHST- 2008/01/25 09:00 [medline]
PHST- 2007/11/16 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - JVI.00736-07 [pii]
AID - 0736-07 [pii]
AID - 10.1128/JVI.00736-07 [doi]
PST - ppublish
SO  - J Virol. 2008 Jan;82(2):710-8. doi: 10.1128/JVI.00736-07. Epub 2007 Nov 14.