title: LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones.
abstract: The rat glucocorticoid receptor confers hormone-dependent transcriptional enhancement when expressed in yeast, thereby enabling the genetic identification of nonreceptor proteins that function in the hormone signal-transduction pathway. We isolated a yeast mutant, lem1, with increased sensitivity to dexamethasone and triamcinolone acetonide; responsiveness to a third agonist, deoxycorticosterone, is unaffected. Cloning of wild-type LEM1 revealed a putative transport protein of the ATP-binding cassette family. Dexamethasone accumulation is increased in lem1 cells, suggesting that wild-type LEM1 decreases dexamethasone potency by exporting this ligand. LEM1 appears to affect certain steroids and not others. We propose that transporters like LEM1 can selectively modulate the intracellular levels of steroid hormones. Differential activities of such transporters in mammalian cells might regulate hormone availability and thereby hormone signaling in a cell-type specific manner.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0448, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kralli
authors.forename: S P
authors.initials: SP
authors.lastname: Bohen
authors.forename: K R
authors.initials: KR
authors.lastname: Yamamoto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005816:Genetic Complementation Test; D007700:Kinetics; D008322:Mammals; D016296:Mutagenesis; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014222:Triamcinolone Acetonide / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; C092438:PDR5 protein, S cerevisiae; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D003900:Desoxycorticosterone; D004958:Estradiol; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D005020:Ethyl Methanesulfonate; D014222:Triamcinolone Acetonide