Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells

Resistance of tumor cells to multiple cytotoxic drugs is a major impediment to cancer chemotherapy

Chang-jie Chen; Janice E. Chin; Kazumitsu Ueda; Douglas P. Clark; Ira Pastan; Michael M. Gottesman; Igor B. Roninson

2004

Scholarcy highlights

  • 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
  • Complete primary structure of human P-glycoprotein has been determined from the cDNA sequence
  • 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 multi-drug-resistant cells
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