Mammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins

doi:10.1016/0092-8674(86)90594-5

Cell

Volume 47, Issue 3, 7 November 1986, Pages 371-380

https://doi.org/10.1016/0092-8674(86)90594-5 Get rights and content

Abstract

The complete nucleotide and primary structure (1276 amino acids) of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented. The deduced amino acid sequence suggests that mdr is a membrane glycoprotein which includes six pairs of transmembrane domains and a cluster of potentially N-linked glycosylation sites near the amino terminus. A striking feature of the protein is an internal duplication that includes approximately 500 amino acids. Each duplicated segment includes a consensus ATP-binding site. Amino acid homology is observed between the mdr gene and a series of bacterial transport genes. This strong homology suggests that a highly conserved functional unit involved in membrane transport is present in the mdr polypeptide. We propose that an energy-dependent transport mechanism is responsible for the multidrug-resistant phenotype.

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Cell

ArticleMammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins

Abstract

Trends Biochem. Sci.

Gene

J. Biol. Chem.

Biochem. Biophys. Acta

J. Mol. Biol.

J. Biol. Chem.

Isolation and genetic characterization of human KB cell lines resistant to multiple drugs

Somatic Cell Mol. Genet

Correlation of double minute chromosomes with unstable multidrug cross-resistance in uptake mutants of neuroblastoma cells

Altered surface membrane glycoproteins in vinca alkaloid-resistant human leukemic lymphoblasts

Cancer Res.

Isolation and characterization of an anthracycline-resistant human leukemic cell line

Cancer Res.

Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic and cytogenetic studies

Cancer Res.

Drug resistance in Chinese hamster lung and mouse tumor cells

Cancer Treat. Rep.

Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150–170 kDa protein detected by photoaffinity labeling

Active outward transport of daunomycin in resistant ehrilich ascites tumor cells

Bioch. Biophys. Acta.

A model of evolutionary change in protein

Survey of new data and computer methods of analysis

Establishing homologies in protein sequences

Meth. Enzymol.

A comprehensive set of sequence analysis programs for the VAX

Nucl. Acids Res.

Domainal evolution of a prokaryotic DNA-repair protein and its relationship to active transport proteins

Nature

Nucleotide sequence of an Escherichia coli chromosomal hemolysin

J. Bacteriol.

Amplification of DNA sequences in human multidrug-resistant KB carcinoma cells

Reduced drug accumulation in multiply drug-resistant human KB carcinoma cell lines

Cancer Res.

Genetic recombination and molecular cloning of the tripeptide (tpp) gene of Salmonella typhimurium

J. Bacteriol.

Sequence of the malK gene in E. coli K12

Nucl. Acids Res.

Isolation and characterization of DNA sequences amplified in multidrug resistant hamster cells

Chromosome mediated gene transfer of multidrug resistance

Mol. Cell. Biol.

Isolation and expression of a cDNA (mdr) that confers multidrug resistance

Nature

Correlation of unstable multidrug cross resistance in Chinese hamster ovary cells with a homogeneously staining region on chromosome 1

Mol. Cell. Biol.

Article
Mammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins