Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes

Masakiyo Hosokawa, Tomomi Furihata, Yumiko Yaginuma, Naoko Yamamoto, Nao Koyano, Ayako Fujii, Yuko Nagahara, Testuo Satoh, Kan Chiba

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71 Scopus citations

Abstract

The mammalian carboxylesterases (CESs) comprise a multigene family which gene products play important roles in biotransformation of ester- or amide-type prodrugs. Since expression level of CESs may affect the pharmacokinetic behavior of prodrugs in vivo, it is important to understand the transcriptional regulation mechanism of the CES genes. However, little is known about the gene structure and transcriptional regulation of the mammalian CES genes. In the present study, to investigate the transcriptional regulation of the promoter region of the CES1 and CES2 genes were isolated from mouse, rat and human genomic DNA by PCR amplification. A TATA box was not found the transcriptional start site of all CES promoter. These CES promoters share several common binding sites for transcription factors among the same CES families, suggesting that the orthologous CES genes have evolutionally conserved transcriptional regulatory mechanisms. The result of present study suggested that the mammalian CES promoters were at least partly conserved among the same CES families, and some of the transcription factors may play similar roles in transcriptional regulation of the human and murine CES genes.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalDrug Metabolism Reviews
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Carboxylesterase (CES)
  • Prodrug
  • Promoter
  • Transcriptional regulation

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