The ABC transporter Abcg2/Bcrp: role in hypoxia mediated survival.
ABC (ATP-binding cassette) transporters have diverse roles in many cellular processes. These diverse roles require the presence of conserved membrane spanning domains and nucleotide binding domains. Bcrp (Abcg2) is a member of the ATP binding cassette family of plasma membrane transporters that was originally discovered for its ability to confer drug resistance in tumor cells. Subsequent studies showed Bcrp expression in normal tissues and high expression in primitive stem cells. Bcrp expression is induced under low oxygen conditions consistent with its high expression in tissues exposed to low oxygen environments. Moreover, Bcrp interacts with heme and other porphyrins. This finding and its regulation by hypoxia suggests it may play a role in protecting cells/tissue from protoporphyrin accumulation under hypoxia. These observations are strengthened by the fact that porphyrins accumulate in tissues of the Bcrp knockout mouse. It is possible that humans with loss of function Bcrp alleles may be more susceptible to porphyrin-induced phototoxicity. We propose that Bcrp plays a role in porphyrin homoeostasis and regulates survival under low oxygen conditions.
Krishnamurthy
Partha
P
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale Ave., Memphis, TN 38105-2794 , USA.
Schuetz
John D
JD
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000483:Alleles; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D003676:Deferoxamine / Q000378:metabolism; D006418:Heme / Q000737:chemistry*; D006801:Humans; D000860:Hypoxia; D008956:Models, Chemical; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D014018:Tissue Distribution
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D011166:Porphyrins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006418:Heme; D000255:Adenosine Triphosphate; D003676:Deferoxamine; D010100:Oxygen