RRC ID 31703
Author Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB.
Title Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells.
Journal Cell
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.
Volume 47(3)
Pages 381-9
Published 1986-11-7
DOI 10.1016/0092-8674(86)90595-7
PII 0092-8674(86)90595-7
PMID 2876781
MeSH 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
IF 38.637
Times Cited 1861
DNA material Human MDR1 cDNA (RDB01372)