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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-22
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pubmed:abstractText |
The genetic basis for the Ara-C resistance of CCRF-CEM Ara-C/8C leukemia cells was investigated. DNA sequencing revealed that these cells expressed an equilibrative nucleoside transporter 1 (ENT1) with a single missense mutation resulting in glycine to arginine replacement (G24R). To test the importance of this residue, additional G24 mutants were created and examined for [3H]-uridine and [3H]-Ara-C uptake. Both a G24E and G24A mutant showed reduced ENT1-dependent activity. An EGFP-tagged G24R ENT1 displayed plasma membrane localization even though it was unable to bind [3H]-NBMPR, an ENT1-specific inhibitor. These results define G24 as critical amino acid for ENT1 nucleoside uptake and suggest that mutations in TM1 may provide a mechanism for Ara-C resistance in CCRF-CEM Ara-C/8C cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-10722669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-10763851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-11584005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-11814344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-12416024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-12538831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-12838422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-14737075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-15037197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-15510196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-15632314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-15649894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-15701636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-16099839,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-16818276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-17121826,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-18381442,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-2558543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-2842332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-9058027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19116148-9207471
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-nitrobenzylthioinosine,
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/Equilibrative Nucleoside...,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/SLC29A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thioinosine
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1873-3468
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
583
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
425-9
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pubmed:dateRevised |
2010-9-22
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pubmed:meshHeading |
pubmed-meshheading:19116148-Amino Acid Sequence,
pubmed-meshheading:19116148-Animals,
pubmed-meshheading:19116148-Antimetabolites, Antineoplastic,
pubmed-meshheading:19116148-Cell Line, Tumor,
pubmed-meshheading:19116148-Cell Membrane,
pubmed-meshheading:19116148-Cytarabine,
pubmed-meshheading:19116148-Drug Resistance, Neoplasm,
pubmed-meshheading:19116148-Equilibrative Nucleoside Transporter 1,
pubmed-meshheading:19116148-Glycine,
pubmed-meshheading:19116148-Humans,
pubmed-meshheading:19116148-Leukemia, T-Cell,
pubmed-meshheading:19116148-Molecular Sequence Data,
pubmed-meshheading:19116148-Point Mutation,
pubmed-meshheading:19116148-Protein Structure, Tertiary,
pubmed-meshheading:19116148-RNA, Messenger,
pubmed-meshheading:19116148-Thioinosine
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pubmed:year |
2009
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pubmed:articleTitle |
Identification of a novel point mutation in ENT1 that confers resistance to Ara-C in human T cell leukemia CCRF-CEM cells.
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pubmed:affiliation |
Department of Pharmacology, 4009 Genetic Medicine Bldg., 120 Mason Farm Rd. CB# 7365, University of North Carolina @ Chapel Hill, Chapel Hill, NC 27599-7365, United States.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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