NDLI: Human deoxycytidine kinase is located in the cell nucleus.

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Human deoxycytidine kinase is located in the cell nucleus.

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Human deoxycytidine kinase is located in the cell nucleus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Brismar, S. Karlsson, A. Johansson, M.
Description	Author Affiliation: Johansson M ( Medical Nobel Institute, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden.);
Abstract	Human deoxyribonucleoside kinases are required for the pharmacological activity of several clinically important anticancer and antiviral nucleoside analogs. Human deoxycytidine kinase and thymidine kinase 1 are described as cytosolic enzymes in the literature, whereas human deoxyguanosine kinase and thymidine kinase 2 are believed to be located in the mitochondria. We expressed the four human deoxyribonucleoside kinases as fusion proteins with the green fluorescent protein to study their intracellular locations in vivo. Our data showed that the human deoxycytidine kinase is located in the cell nucleus and the human deoxyguanosine kinase is located in the mitochondria. The fusion proteins between green fluorescent protein and thymidine kinases 1 and 2 were both predominantly located in the cytosol. Site-directed mutagenesis of a putative nuclear targeting signal, identified in the primary structure of deoxycytidine kinase, completely abolished nuclear import of the protein. Reconstitution of a deoxycytidine kinase-deficient cell line with the wild-type nuclear or the mutant cytosolic enzymes both restored sensitivity toward anticancer nucleoside analogs. This paper reports that a deoxyribonucleoside kinase is located in the cell nucleus and we discuss the implications for deoxyribonucleotide synthesis and phosphorylation of nucleoside analogs.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	22
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Nucleus Enzymology Deoxycytidine Kinase Isolation & Purification Amino Acid Sequence Cell Compartmentation Drug Effects Cladribine Pharmacology Cytarabine Genetics Dose-Response Relationship, Drug Green Fluorescent Proteins Luminescent Proteins Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Localization Signals Nucleosides Recombinant Fusion Proteins Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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