The dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response.
The Drosophila homolog of the retinoid X receptor, ultraspiracle (USP), heterodimerizes with the ecdysone receptor (EcR) to form a functional complex that mediates the effects of the steroid molting hormone ecdysone by activating and repressing expression of ecdysone response genes. As with other retinoid X receptor heterodimers, EcR/USP affects gene transcription in a ligand-modulated manner. We used in vivo, cell culture, and biochemical approaches to analyze the functions of two usp alleles, usp(3) and usp(4), which encode stable proteins with defective DNA-binding domains. We observed that USP is able to activate as well as repress the Z1 isoform of the ecdysone-responsive broad complex (BrC-Z1). Activation of BrC-Z1 as well as EcR, itself an ecdysone response gene, can be mediated by both the USP3 and USP4 mutant proteins. USP3 and USP4 also activate an ecdysone-responsive element, hsp27EcRE, in cultured cells. These results differ from the protein null allele, usp(2), which is unable to mediate activation [Schubiger, M. & Truman, J. W. (2000) Development 127, 1151--1159]. BrC-Z1 repression is compromised in all three usp alleles, suggesting that repression involves the association of USP with DNA. Our results distinguish two mechanisms by which USP modulates the properties of EcR: one that involves the USP DNA-binding domain and one that can be achieved solely through the ligand-binding domain. These newly revealed properties of USP might implicate similar properties for retinoid X receptor.
Department of Biology, University of California at San Diego, La Jolla, CA 92093, USA.
N
N
Ghbeish
C C
CC
Tsai
M
M
Schubiger
J Y
JY
Zhou
R M
RM
Evans
M
M
McKeown
D000483:Alleles; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000187:drug effects* / Q000502:physiology; D029721:Drosophila Proteins; D004440:Ecdysone / Q000494:pharmacology*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology; D047488:Retinoid X Receptors; D013963:Thyroid Hormones / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014212:Tretinoin / Q000502:physiology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D013963:Thyroid Hormones; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; D004440:Ecdysone; D014212:Tretinoin; D004247:DNA