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Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity.

Publication ,  Journal Article
Forrest, GL; Akman, S; Doroshow, J; Rivera, H; Kaplan, WD
Published in: Mol Pharmacol
October 1991

Carbonyl reductase (NADPH: secondary-alcohol oxidoreductase; EC 1.1.1.184), a widely distributed NADPH-dependent enzyme considered as both an aldo-keto reductase and a quinone reductase, was cloned from a human liver genomic library and transiently expressed in COS7 cells. The gene contains 3142 bases comprising three exons and two introns. The absence of a CAAT and TATA box and the presence of a GC-rich island are characteristic of many "housekeeping" genes. Transient expression of the genomic gene in COS7 cells using an expression vector containing an SV40 origin of replication resulted in a greater than 50-fold increase in both menadione reductase activity and daunorubicin reductase activity, suggesting that both activities are derived from the same enzyme. Carbonyl reductase mRNA levels reflected enzyme activity levels in the transfected cells. Other parameters, such as pH profile, cofactor requirements, substrates, and inhibitors, were similar to those of carbonyl reductase purified by other investigators. Potential regulatory elements with consensus sequences for two GC boxes and the transcriptional activator protein AP-2 were present upstream of the transcriptional start site. Although the precise role of carbonyl reductase is unknown, the enzyme is involved in drug metabolism and in the reduction of activated carbonyl compounds. Its ability to act as a quinone reductase also implies a potential to modulate oxygen free radicals.

Duke Scholars

Published In

Mol Pharmacol

ISSN

0026-895X

Publication Date

October 1991

Volume

40

Issue

4

Start / End Page

502 / 507

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Pharmacology & Pharmacy
  • Molecular Sequence Data
  • Liver
  • Kinetics
  • Humans
  • Genome
  • Gene Expression
  • Cloning, Molecular
  • Base Sequence
 

Citation

APA
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ICMJE
MLA
NLM
Forrest, G. L., Akman, S., Doroshow, J., Rivera, H., & Kaplan, W. D. (1991). Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. Mol Pharmacol, 40(4), 502–507.
Forrest, G. L., S. Akman, J. Doroshow, H. Rivera, and W. D. Kaplan. “Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity.Mol Pharmacol 40, no. 4 (October 1991): 502–7.
Forrest GL, Akman S, Doroshow J, Rivera H, Kaplan WD. Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. Mol Pharmacol. 1991 Oct;40(4):502–7.
Forrest, G. L., et al. “Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity.Mol Pharmacol, vol. 40, no. 4, Oct. 1991, pp. 502–07.
Forrest GL, Akman S, Doroshow J, Rivera H, Kaplan WD. Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. Mol Pharmacol. 1991 Oct;40(4):502–507.

Published In

Mol Pharmacol

ISSN

0026-895X

Publication Date

October 1991

Volume

40

Issue

4

Start / End Page

502 / 507

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Pharmacology & Pharmacy
  • Molecular Sequence Data
  • Liver
  • Kinetics
  • Humans
  • Genome
  • Gene Expression
  • Cloning, Molecular
  • Base Sequence