Internal Duplication and Homology With Bacterial Transport Proteins in the mdr1 (P-glycoprotein) Gene From Multidrug-Resistant Human Cells

Cell. 1986 Nov 7;47(3):381-9. doi: 10.1016/0092-8674(86)90595-7.

Abstract

Resistance of tumor cells to multiple cytotoxic drugs is a major impediment to cancer chemotherapy. Multidrug resistance in human cells is determined by the mdr1 gene, encoding a high molecular weight membrane glycoprotein (P-glycoprotein). Complete primary structure of human P-glycoprotein has been determined from the cDNA sequence. The protein, 1280 amino acids long, consists of two homologous parts of approximately equal length. Each half of the protein includes a hydrophobic region with six predicted transmembrane segments and a hydrophilic region. The hydrophilic regions share homology with peripheral membrane components of bacterial active transport systems and include potential nucleotide-binding sites. These results are consistent with a function for P-glycoprotein as an energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Amino Acid Sequence
  • Bacterial Proteins / analysis
  • Bacterial Proteins / genetics*
  • Base Sequence
  • Biological Transport, Active
  • Cell Line
  • DNA / analysis
  • Drug Resistance / genetics*
  • Glycoproteins / analysis
  • Glycoproteins / genetics*
  • Humans
  • Molecular Weight
  • Neoplasms / drug therapy
  • Protein Conformation

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Bacterial Proteins
  • Glycoproteins
  • DNA

Associated data

  • GENBANK/M14758
  • GENBANK/M14759