Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027819 (
neuroblastoma
)
27,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine and cytidine as well as the pharmacological activation of several cytotoxic pyrimidine ribonucleoside analogues. In this study, we investigated the functional role of two isoforms of UCK in
neuroblastoma
cell lines. Analysis of mRNA coding for
UCK1
and UCK2 showed that UCK2 is the most abundantly expressed UCK in a panel of
neuroblastoma
cell lines. Transient and stable overexpression of UCK2 in
neuroblastoma
cells increased the metabolism of uridine and cytidine as well as the cytotoxicity of 3-deazauridine. Knockdown of endogenous UCK2 as well as overexpression of
UCK1
resulted in decreased metabolism of uridine and cytidine and protected the
neuroblastoma
cells from 3-deazauridine-induced toxicity. Subcellular localization studies showed that
UCK1
-GFP and UCK2-GFP were localized in the cell nucleus and cytosol, respectively. However, co-expression of
UCK1
with UCK2 resulted in a nuclear localization of UCK2 instead of its normal cytosolic localization, thereby impairing its normal function. The physical association of
UCK1
and UCK2 was further demonstrated through pull-down analysis using his-tagged UCK. The discovery that UCK2 is highly expressed in
neuroblastoma
opens the possibility for selectively targeting
neuroblastoma
cells using UCK2-dependent pyrimidine analogues, while sparing normal tissues.
...
PMID:The pivotal role of uridine-cytidine kinases in pyrimidine metabolism and activation of cytotoxic nucleoside analogues in neuroblastoma. 2723 1
Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine, cytidine, and several pyrimidine ribonucleoside analogs. We overexpressed and purified the two known isoforms of human UCK in Escherichia coli, produced a specific antibody against
UCK1
and characterized the kinetic properties of
UCK1
and 2. The V
max
of purified recombinant UCK2 was 22- and 8-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant
UCK1
enzyme. The K
m
of
UCK1
was 39- and 40-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK2 enzyme. The
UCK1
antibody showed no cross reactivity against UCK2. Our data showed that
UCK1
and 2 are both expressed in several
neuroblastoma
cell lines, including four MYCN single copy cell lines and five MYCN amplified cell lines, with the exception that
UCK1
was not expressed in SJNB8. These results indicate that UCK2 in
neuroblastoma
might be used as a selective target for chemotherapy using UCK2-dependent pyrimidine analogues.
...
PMID:Purification, activity, and expression levels of two uridine-cytidine kinase isoforms in neuroblastoma cell lines. 2790 29
