Eukaryotic Mdr1/P-Glycoprotein Homologues: Unconventional Secretion Processes Mediated by a Growing Family of ATP-Dependent Membrane Translocators
Mdr1/P-glycoprotein, when overexpressed, can confer resistance of human tumor cells to multiple lipophilic cytotoxic drugs and this resistance is a major problem in cancer chemotherapy. When mouse and human mdr cDNAs were cloned and sequenced (10,17), one of the intriguing findings was that they showed homology to a family of bacterial active transport systems, including for example the E. coli hlyB gene, whose product is a membrane protein involved in the export of a hemolysin. This observation was the start of what has since been a very active and fruitful area of research, and in the past few years many Mdr/P-glycoprotein homologues have been identified in eukaryotes.
KeywordsPolypeptide Doxorubicin Methotrexate Malaria Oligosaccharide
Unable to display preview. Download preview PDF.
- 8.Brake AJ, Brenner C, Najarian R, Laybourn P, Merryweather J (1985) Structure of genes encoding precursors of the yeast peptide mating pheromone a-factor. In Gething MJ (ed) Protein Transport and Secretion. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 103–108Google Scholar
- 26.Kuchler K, Thorner J (1992) Secretion of peptides and proteins lacking hydrophobic signal sequences: The role of adenosine triphosphate-driven membrane transloca-tors. Endocrine Reviews 13: in pressGoogle Scholar
- 27.Kuchler K, Thorner J (1992) The a-factor transporter (STE6 gene product) and cell polarity in the yeast Saccharomyces cerevisiae. J Cell Biol: in pressGoogle Scholar
- 34.Riordan JR, Rommens JM, Kerem B-S, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou J-L, Drumm ML, Iannuzzi MC, Collins FS, Tsui L-C (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245: 1066–1073PubMedCrossRefGoogle Scholar
- 38.Sterne RE (1989) A novel pathway for peptide hormone biogenesis: processing and secretion of the mating pheromone, a-factor, by Saccharomyces cerevisiae. ph D Thesis, University of California, BerkeleyGoogle Scholar
- 40.Wang M, Balzi E, Van Dyck L, Golin J, Goffeau A (1992) Sequencing of the yeast multidrug resistance PDR5 gene encoding a putative pump for arug efflux. Abstract, 16th Int. Conf. on Yeast Genetics and Molecular BiologyGoogle Scholar