Structural organization and characterization of the regulatory element of the human carboxylesterase (CES1A1 and CES1A2) genes.
Mammalian carboxylesterases comprise a multigene family, the gene products of which are localized in the endoplasmic reticulum. The carboxylesterases catalyze the hydrolysis of various xenobiotics and endogenous substrates such as ester, amide and thioester bonds and are thought to function mainly in drug metabolism. We have suggested the possibility that individual variation of human liver carboxylesterase activity causes the difference in expression levels of CES1A isozymes. However, little is known about the transcriptional regulation of human carboxylesterase genes. In the present study, we isolated two CES genes encoding human carboxylesterase CES1A, which were designated as CES1A1 (AB119997) and CES1A2 (AB119998). These genes were identical except for exon 1 and the 5' regulatory element. We investigated the transcriptional regulation of these two CES genes. A reporter gene assay and electrophoretic mobility shift assay demonstrated that Sp1 and C/EBPalpha could bind to each responsive element of the CES1A1 promoter but that the Sp1 and C/EBP could not bind to the responsive element of the CES1A2 promoter. Thus, CES1A1 mRNA expression level is much higher than the expression level of CES1A2 mRNA in the liver and lung. It is thought that these results provide information on individual variation of human carboxylesterase isozymes.
Hosokawa
Masakiyo
M
Laboratory of Drug Metabolism and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba Institute of Sciences, Choshi, Japan. masakiyo@cis.ac.jp
Furihata
Tomomi
T
Yaginuma
Yumiko
Y
Yamamoto
Naoko
N
Watanabe
Natsuko
N
Tsukada
Eiko
E
Ohhata
Yoshiko
Y
Kobayashi
Kaoru
K
Satoh
Testuo
T
Chiba
Kan
K
D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D043182:Carboxylesterase / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D002265:Carboxylic Ester Hydrolases
D020121:5' Untranslated Regions; D043182:Carboxylesterase; D007527:Isoenzymes; D012333:RNA, Messenger; C474609:CES1 protein, human; D002265:Carboxylic Ester Hydrolases