Induction of choline kinase alpha by carbon tetrachloride (CCl4) occurs via increased binding of c-jun to an AP-1 element.
The mechanism by which treatment of mice with CCl4 induces an increase in choline kinase alpha has been investigated. Nuclear run on assays demonstrated a major increase in the transcript for choline kinase alpha in livers from mice 3 h and 6 h after administration of CCl4 compared to vehicle (olive oil). 5'deletion analyses of choline kinase alpha promoter-luciferase constructs expressed in Hepa-1 cells identified a promoter element between -875 and -866 that was nearly identical to an AP-1 consensus site. Mutation of this AP-1 site caused a striking decrease in the expression of choline kinase alpha promoter-luciferase constructs. Electromobility shift assays with nuclear extracts from mouse liver demonstrated that c-Jun, but not c-fos, bound oligonucleotides with the AP-1 site. The amount of c-jun bound was greatly increased when hepatic nuclear extracts from mice treated with CCl4 were used. Chromatin immunoprecipitation assays confirmed that c-jun binds to the choline kinase alpha promoter. The results from these studies provide strong evidence that the choline kinase alpha promoter has a distal element (-875/-867) that binds c-jun and the binding of c-jun is enhanced by treatment with CCl4.
Aoyama
Chieko
C
Department of Biochemistry and the Canadian Institutes of Health Research Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. caoyama@dokkyomed.ac.jp
Ishidate
Kozo
K
Sugimoto
Hiroyuki
H
Vance
Dennis E
DE
D000818:Animals; D001483:Base Sequence; D002251:Carbon Tetrachloride / Q000378:metabolism*; D045744:Cell Line, Tumor; D002797:Choline Kinase / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D012997:Solvents; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D007527:Isoenzymes; D016755:Proto-Oncogene Proteins c-jun; D012997:Solvents; D018808:Transcription Factor AP-1; D002251:Carbon Tetrachloride; D002797:Choline Kinase