Involvement of protein kinase in environmental stress-induced activation of human multidrug resistance 1 (MDR1) gene promoter

Takeshi Uchiumi, Kimitoshi Kohno, Hideyuki Tanimura, Katsuhiko Hidaka, Keizo Asakuno, Hiroko Abe, Yuzo Uchida, Michihiko Kuwano

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53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11-16
Number of pages6
JournalFEBS Letters
Volume326
Issue number1-3
DOIs
Publication statusPublished - Jul 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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