Isolation and characterization of Drosophila multidrug resistance gene homologs.
Mammalian multidrug-resistant cell lines, selected for resistance to a single cytotoxic agent, display cross-resistance to a broad spectrum of structurally and functionally unrelated compounds. These cell lines overproduce a membrane protein, the P-glycoprotein, which is encoded by a member(s) of a multigene family, termed mdr or pgp. The amino acid sequence of the P-glycoprotein predicts an energy-dependent transport protein with homology to a large superfamily of proteins which transport a wide variety of substances. This report describes the isolation and characterization of two Drosophila homologs of the mammalian mdr gene. These homologs, located in chromosomal sections 49EF and 65A, encode proteins that share over 40% amino acid identity to the human and murine mdr P-glycoproteins. Fly strains bearing disruptions in the homolog in section 49EF have been constructed and implicate this gene in conferring colchicine resistance to the organism. This work sets the foundation for the molecular and genetic analysis of mdr homologs in Drosophila melanogaster.
Wu
C T
CT
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
Budding
M
M
Griffin
M S
MS
Croop
J M
JM
D018435:ATP Binding Cassette Transporter, Subfamily B; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003078:Colchicine / Q000494:pharmacology; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004330:Drosophila / Q000187:drug effects / Q000235:genetics*; D029721:Drosophila Proteins; D004351:Drug Resistance / Q000235:genetics*; D015723:Gene Library; D006801:Humans; D007301:Insect Hormones / Q000235:genetics*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation; D009693:Nucleic Acid Hybridization; D012689:Sequence Homology, Nucleic Acid
D018435:ATP Binding Cassette Transporter, Subfamily B; D003078:Colchicine; D004247:DNA; D029721:Drosophila Proteins; D007301:Insect Hormones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C069936:mdr65 protein, Drosophila; C069935:mdr49 protein, Drosophila