Cloning and initial characterization of the human DPYD gene promoter

Détails

ID Serval
serval:BIB_CA9E7D12F6B9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cloning and initial characterization of the human DPYD gene promoter
Périodique
Biochemical and Biophysical Research Communications
Auteur(s)
Collie-Duguid  E. S., Johnston  S. J., Powrie  R. H., Milano  G., Etienne  M. C., Rochat  B., Watson  G. C., McLeod  H. L.
ISSN
0006-291X (Print)
Statut éditorial
Publié
Date de publication
04/2000
Volume
271
Numéro
1
Pages
28-35
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr 29
Résumé
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and pyrimidine-based antimetabolites. Reduced DPD activity is associated with toxicity to 5-fluorouracil (5FU) therapy in cancer patients and with neurological abnormalities in paediatric patients. Although variant DPYD alleles have been identified in DPD-deficient patients, they do not adequately explain polymorphic DPD activity or associated clinical phenotypes in vivo. DPD may be transcriptionally regulated as mRNA levels correlate with activity and are differentially regulated in human tissues. A 1.85 kb 5' flanking region of the human DPYD gene was cloned and has transcriptional activity in cultured cells. Analysis of this 5' flanking region in rhesus and cynomolgus monkeys demonstrated conservation (>96%) between humans and primates. Putative binding sites for ubiquitous and cell-specific factors were identified. A polymorphism that disrupts a putative gamma-interferon response element was identified in a cancer patient with reduced DPD activity and severe 5FU toxicity. Further insight into regulation of DPD expression may identify new avenues for the treatment of clinical problems associated with DPD deficiency.
Mots-clé
Animals Base Sequence Cloning, Molecular Conserved Sequence Dihydrouracil Dehydrogenase (NADP) Humans Liver/metabolism Macaca fascicularis Macaca mulatta Molecular Sequence Data Neoplasms/blood Oxidoreductases/*genetics/metabolism Phylogeny Polymerase Chain Reaction Polymorphism, Restriction Fragment Length *Promoter Regions (Genetics) Protein Biosynthesis Sequence Homology, Nucleic Acid Transfection Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
25/01/2008 9:47
Dernière modification de la notice
03/03/2018 21:25
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