LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones

Anastasia Kralli, Sean P. Bohen, Keith R. Yamamoto

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4701-4705
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number10
DOIs
StatePublished - May 9 1995
Externally publishedYes

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Keywords

  • PDR5
  • STS1
  • glucocorticoid receptor
  • yeast

ASJC Scopus subject areas

  • General

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