ArticleJournal of virology1998
Differential intracellular compartmentalization of herpetic thymidine kinases (TKs) in TK gene-transfected tumor cells: molecular characterization of the nuclear localization signal of herpes simplex virus type 1 TK.
Article in Journal of virology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- ERK-dependent suicide gene therapy for selective targeting of RTK/RAS-driven cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- High-efficiency nonhomologous insertion of a foreign gene into the herpes simplex virus genome.The Journal of general virology · 2020Article
- KSHV-TK is a tyrosine kinase that disrupts focal adhesions and induces Rho-mediated cell contraction.The EMBO journal · 2015Article
- Suicide Gene Therapy for Cancer - Current Strategies.Journal of genetic syndromes & gene therapy · 2013Article
- A transgenic tri-modality reporter mouse.PloS one · 2013Article
- Characterization of the subcellular localization of herpes simplex virus type 1 proteins in living cells.Medical microbiology and immunology · 2011Article
- The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures.Medicinal research reviews · 2011Review
- Rana grylio virus thymidine kinase gene: an early gene of iridovirus encoding for a cytoplasmic protein.Virus genes · 2009Article
- Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future.Medicinal research reviews · 2008Review
- Epstein-Barr virus thymidine kinase is a centrosomal resident precisely localized to the periphery of centrioles.Journal of virology · 2007Article
- Expression and functional characterization of the putative protein 8b of the severe acute respiratory syndrome-associated coronavirus.FEBS letters · 2006Article
- Functional divergence of Kaposi's sarcoma-associated herpesvirus and related gamma-2 herpesvirus thymidine kinases: novel cytoplasmic phosphoproteins that alter cellular morphology and disrupt adhesion.Journal of virology · 2005Article
- Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.Antimicrobial agents and chemotherapy · 2005Article
- Imaging tri-fusion multimodality reporter gene expression in living subjects.Cancer research · 2004Article
- A novel 'sort-suicide' fusion gene vector for T cell manipulation.Gene therapy · 2002Article
- Article
- Selection of HSV-1 TK gene-transfected murine mammary carcinoma cells resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and ganciclovir (GCV).Gene therapy · 2000Article
- Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues.Gene therapy · 1999Article
- Cytoplasmically retargeted HSV1-tk/GFP reporter gene mutants for optimization of noninvasive molecular-genetic imaging.Neoplasia (New York, N.Y.)Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The thymidine kinases (TKs) of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) were expressed in human osteosarcoma cells as fusion proteins with the green fluorescent protein (GFP), and their intracellular localizations were determined. The three TK-GFP fusion products were localized in different subcellular compartments of the transfected tumor cells. HSV-1 TK-GFP was localized exclusively in the nucleus, HSV-2 TK-GFP was predominantly found in the cytosol, while VZV TK-GFP was localized in both the nucleus and the cytosol. In support of these findings, we identified a nuclear localization signal (NLS) in the N-terminal arginine-rich region of HSV-1 TK that was absent in HSV-2 and VZV TK. The first 34 amino acids proved necessary for the specific nuclear localization of HSV-1 TK and, when added to the VZV TK-GFP gene construct, also sufficed to specifically target VZV TK-GFP to the nucleus. Further analysis of this NLS through site-directed mutagenesis revealed that the basic amino acid-rich nonapeptide 25R-R-T-A-L-R-P-R-R33 is of crucial importance in the nuclear targeting of HSV-1 TK. In particular, we revealed that the presence of the arginine residues at positions 25, 26, 30, 32, and 33 is obligatory for efficient NLS functioning, whereas arginine and histidine residues outside of the nonapeptide (i.e., residues R18, R20, and H22) did not change the functional properties of the NLS.
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