A role for ectophosphatase in xenobiotic resistance.
Xenobiotic resistance in animals, plants, yeast, and bacteria is known to involve ATP binding cassette transporters that efflux invading toxins. We present data from yeast and a higher plant indicating that xenobiotic resistance also involves extracellular ATP degradation. Transgenic upregulation of ecto-ATPase alone confers resistance to organisms that have had no previous exposure to toxins. Similarly, cells that are deficient in extracellular ATPase activity are more sensitive to xenobiotics. On the basis of these and other supporting data, we hypothesize that the hydrolysis of extracellular ATP by phosphatases and ATPases may be necessary for the resistance conferred by P-glycoprotein.
Thomas
C
C
Section of Molecular Cell and Developmental Biology, Biological Laboratories 311, University of Texas at Austin, Texas 78713, USA.
Rajagopal
A
A
Windsor
B
B
Dudler
R
R
Lloyd
A
A
Roux
S J
SJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D001081:Apyrase / Q000235:genetics / Q000378:metabolism; D017360:Arabidopsis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005800:Genes, Fungal; D017343:Genes, Plant; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009550:Nigericin / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018515:Plant Leaves / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D030821:Plants, Genetically Modified; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015262:Xenobiotics / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins; C092438:PDR5 protein, S cerevisiae; D010940:Plant Proteins; D029701:Saccharomyces cerevisiae Proteins; D015262:Xenobiotics; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D001081:Apyrase; D000241:Adenosine; D009550:Nigericin