Linked Life Data

19765547

Source:http://linkedlifedata.com/resource/pubmed/id/19765547

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-11-25
pubmed:abstractText
Deoxycytidine analogs are an important class of clinically active antiviral and anticancer agents. The stepwise phosphorylation of these analogs to triphosphate metabolites is crucial for biological action. Human UMP/CMP kinase (UMP/CMPK; cytidylate kinase; EC 2.7.4.14) is thought to be responsible for phosphorylation of UMP, CMP, and dCMP and may also play an important role in the activation of pyrimidine analogs. However, no evidence has verified this notion in intact cells. In this study we explored the functional roles of UMP/CMPK in natural pyrimidine synthesis and metabolism of deoxycytidine analogs, as well as 5-FU in HeLa S3 and HCT8 cells. The amounts of UMP/CMPK protein in different cell lines correlated with UMP, CMP, and dCMP kinase activities and amounts of UMP/CMPK RNA. Modulation of UMP/CMPK by overexpression or down-regulation had no impact on natural pyrimidine nucleotides and cell growth. However, down-regulating UMP/CMPK expression by siRNA led to a decrease in the formation of the triphosphate metabolites, resulting in cellular resistance to these analogs. More diphosphate and triphosphate metabolites of deoxycytidine analogs were detected and cellular sensitivity to these agents was increased in the UMP/CMPK-overexpressing cells. This study indicates that the second step enzyme (UMP/CMPK) is responsible for the phosphorylation of pyrimidine analogs and also has an impact on cellular sensitivity to these analogs in those cell lines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1873-2968
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
381-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Modulation of human UMP/CMP kinase affects activation and cellular sensitivity of deoxycytidine analogs.
pubmed:affiliation
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan, ROC. jyliou68@nhri.org.tw
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't