Ecdysteroid-dependent regulation of genes in mammalian cells by a Drosophila ecdysone receptor and chimeric transactivators.
Steroid receptors are members of a large family of transcription factors whose activity is tightly regulated by the binding of their cognate steroid ligand. Mammalian steroid hormone receptors have been exploited to obtain the regulated expression of heterologous genes in mammalian cells. However, the utility of these systems in cultured cells and transgenic animals is limited by the presence of endogenous steroids and their receptors. We show that a Drosophila ecdysone receptor can function in cultured mammalian cells as an ecdysteroid-dependent transcription factor. The activity of the ecdysone receptor was not induced by any of the mammalian steroid hormones tested. The DNA-binding and transactivation activities of viral, mammalian, or bacterial proteins were rendered ecdysteroid-dependent when fused to the ligand-binding domain of the ecdysone receptor. The ecdysone receptor may prove useful in selectively regulating the expression of endogenous or heterologous genes in mammalian cells.
Christopherson
K S
KS
Department of Cell Genetics, Genentech, Inc., South San Francisco, CA 94080.
Mark
M R
MR
Bajaj
V
V
Godowski
P J
PJ
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry; D004331:Drosophila melanogaster / Q000235:genetics*; D026461:Ecdysteroids; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D007447:Invertebrate Hormones / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D011987:Receptors, Steroid / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D026461:Ecdysteroids; D007447:Invertebrate Hormones; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C055469:ecdysone receptor