Control of expression of the human glutathione S-transferase pi gene differs from its rat orthologue.
We have examined regulation of the glutathione S-transferase pi gene by transient expression assay, and find that a fragment from 8 to 99 bp upstream of the cap site promotes transcription, but there is no evidence for any enhancer activity in a further 6 kb of flanking sequence. Analysis of this sequence by reference to a primate sequence database and Southern blotting revealed that as much as 5 kb of this flanking DNA were composed of repetitive insertion elements including an Alu and a LINE 1 repeat. The promoter fragment has been sequenced (Cowell et al (1988) Biochem. J. 255, 79-83) and contains a consensus AP1 binding site; in some cases, these have been associated with transcriptional induction by phorbol esters and ras oncogenes. We measured the steady state levels of glutathione S-transferase pi mRNA in human cell lines which were known to express ras oncogenes and compared them to human cell lines which have not been identified with ras activation. There was no correlation between expression of activated ras and expression of glutathione S-transferase pi mRNA. Treatment of HeLa cells, HepG2 cells and a small cell lung carcinoma line, GLC 8, with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate failed to alter the steady state levels of endogenous glutathione S-transferase pi mRNA. The differences between these results and those of similar studies on rat glutathione S-transferase subunit 7, a structural orthologue of glutathione S-transferase pi, are discussed.
Dixon
K H
KH
CRC Molecular Toxicology Research Group, University College and Middlesex School of Medicine, London, UK.
Cowell
I G
IG
Xia
C L
CL
Pemble
S E
SE
Ketterer
B
B
Taylor
J B
JB
D000818:Animals; D015152:Blotting, Northern; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015183:Restriction Mapping; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014158:Transcription, Genetic
D012333:RNA, Messenger; D005982:Glutathione Transferase; D013755:Tetradecanoylphorbol Acetate