Molecular basis for decreased folylpoly-γ-glutamate synthetase expression in a methotrexate resistant CCRF-CEM mutant cell line
| Autor: | Tingting Hsieh-Kinser, Guy J. Leclerc, Teresa York, Julio C. Barredo |
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| Rok vydání: | 2007 |
| Předmět: |
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Molecular Cancer Research Molecular Sequence Data Protein domain Mutant Biology Reduced Folate Carrier Protein Structure-Activity Relationship Cell Line Tumor Humans Leukemia-Lymphoma Adult T-Cell Point Mutation Amino Acid Sequence RNA Messenger Peptide Synthases Promoter Regions Genetic Oligonucleotide Array Sequence Analysis chemistry.chemical_classification Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Point mutation Mutagenesis Nucleic acid sequence Glutamate receptor Membrane Transport Proteins Hematology Molecular biology Phenotype Protein Structure Tertiary Amino acid Enzyme Activation Methotrexate Oncology chemistry Biochemistry Drug Resistance Neoplasm |
| Zdroj: | Leukemia Research. 31:293-299 |
| ISSN: | 0145-2126 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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