LEM1, AN ATP-BINDING-CASSETTE TRANSPORTER, SELECTIVELY MODULATES THE BIOLOGICAL POTENCY OF STEROID-HORMONES

The rat glucocorticoid receptor confers hormone-dependent transcriptio nal enhancement when expressed in yeast, thereby enabling the genetic identification of nonreceptor proteins that function iri the hormone s ignal-transduction pathway. We isolated a yeast mutant, lem1, with inc reased sensitivity to dexamethasone and triamcinolone acetonide; respo nsiveness to a third agonist, deoxycorticosterone, is unaffected. Clon ing of wild-type LEM1 revealed a putative transport protein of the ATP -binding cassette family. Dexamethasone accumulation is increased in l em1 cells, suggesting that wild-type LEM1 decreases dexamethasone pote ncy 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 a ctivities of such transporters in mammalian cells might regulate hormo ne availability and thereby hormone signaling in a cell-type specific manner.