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Involvement of protein kinase in environmental stress‐induced activation of human multidrug resistance 1 (MDR1) gene promoter
Author(s) -
Uchiumi Takeshi,
Kohno Kimitoshi,
Tanimura Hideyuki,
Hidaka Katsuhiko,
Asakuno Keizo,
Abe Hiroko,
Uchida Yuzo,
Kuwano Michihiko
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81750-t
Subject(s) - okadaic acid , chloramphenicol acetyltransferase , promoter , microbiology and biotechnology , gene , biology , protein kinase a , kinase , phosphorylation , chemistry , gene expression , biochemistry , phosphatase
The human MDR1 gene can be induced in response to various environmental stimuli. To examine whether such stress‐induced activation of the MDR1 gene can be modulated by protein kinase, we employed a stable human cancer KB cell line which contained the bacterial chloramphenicol acetyltransferase (CAT) gene directed by the MDR1 gene promoter. H‐7, a protein kinase C inhibitor, at more than 40 μM inhibited activation of the MDR1 promoter that was induced by ethylmethane sulfonate, 5‐fluorouracil or UV irradiation. DNA binding activity of nuclear factors recognizing the MDR1 promoter was augmented in KB cells treated with UV, but decreased in cells treated concomitantly with H‐7. Okadaic acid alone was able to induce the promoter activation, and this induction was dependent on specific promoter sequences. Okadaic acid also enhanced the DNA binding activity of nuclear factors recognizing the MDR1 promoter. The phosphorylation of transacting factors may modulate the MDR1 gene promoter activity.