Molecular basis for decreased folylpoly-gamma-glutamate synthetase expression in a methotrexate resistant CCRF-CEM mutant cell line.
Leuk Res
; 31(3): 293-9, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-16884772
ABSTRACT
A CCRF-CEM mutant, CEM-p, has been shown to exhibit resistance to methotrexate due to decreased methotrexate polyglutamate accumulation. To ascertain the mechanism(s) responsible for this phenotype, we analyzed FPGS and SLC19A1 mRNA expression, examined FPGS promoter activity, and determined nucleotide sequence of the FPGS promoter and full length cDNA from CCRF-CEM and CEM-p cells. We identified in FPGS from CEM-p cells three amino acid substitutions that altered the ATP binding P-loop, glutamate/folate binding, and a conserved domain located at the carboxyl-terminal. Our data demonstrated for the first time the importance of the highly conserved domain (VTGSLHLVGGV) located at the carboxyl-terminal for FPGS activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
/
Leucemia-Linfoma de Células T do Adulto
/
Metotrexato
/
Mutação Puntual
/
Perfilação da Expressão Gênica
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2007
Tipo de documento:
Article