Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug daunorubicin

Ge Zhou, M. Tien Kuo

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The expression of P-glycoproteins encoded by the mdr gene family is associated with the emergence of the multidrug resistance phenotype in animal cella mdr expression can be induced by many extracellular stimulants including cytotoxic drugs and chemical carcinogens. However, little is known about the mechanisms involved. Here, we report that the expression of the rat mdr1b can be induced by anticancer drug daunorubicin. Further analysis identified a bona fide p53-binding site spanning from base pairs - 199 to - 180 (5'-GAACATGTAGAGACATGTCT-3') in the rat mdr1b promoter that is essential for basal and daunorubicin-inducible promoter activities. In addition, our results show that wildtype p53 can up-regulate not only the promoter function but also endogenous expression of the rat mdr1b. To the best of our knowledge, this is the first report showing that a specific p58-binding site is involved in the transcriptional regulation of mdr gene by wild-type p53. Since p58 is a sensor for a wide variety of genotoxic stresses, our finding has broad implications for understanding the mechanisms involved in the inducible expression of mdr gene by anticancer drugs, chemical carcinogens, UV light, and other DNA-damaging agents.

Original languageEnglish (US)
Pages (from-to)15387-15394
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number25
DOIs
StatePublished - Jun 19 1998

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Daunorubicin
Rats
Genes
Carcinogens
Binding Sites
Pharmaceutical Preparations
P-Glycoproteins
p53 Genes
Multiple Drug Resistance
Ultraviolet Rays
Base Pairing
Ultraviolet radiation
DNA Damage
Animals
Up-Regulation
Phenotype
Gene Expression
DNA
Sensors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug daunorubicin. / Zhou, Ge; Kuo, M. Tien.

In: Journal of Biological Chemistry, Vol. 273, No. 25, 19.06.1998, p. 15387-15394.

Research output: Contribution to journalArticle

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