A Receptor Without a Ligand

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Science  13 Jun 2003:
Vol. 300, Issue 5626, pp. 1623
DOI: 10.1126/science.300.5626.1623c

The insect hormone α-ecdysone is considered to be the major trigger of morphogenic change during Drosophila larval development and entry into metamorphosis. Its actions are mediated through a heterodimer complex consisting of two nuclear receptors: the ecdysteroid receptor (EcR) and Ultraspiracle (USP). Nevertheless, the presence of other ecdysteroids in insect hemolymph at specific developmental stages has raised the question of whether and how these other compounds might function.

Only one other Drosophila nuclear receptor, DHR38, is known to form a complex with USP. Baker et al. now show that a DHR38-USP complex governs a second ecdysteroid signaling pathway. Several naturally occurring Drosophila ecdysteroids stimulated DHR38-dependent transcription in cultured Drosophila cells, but only when the receptor formed heterodimers with a constitutively activated form of USP. Hence, unlike EcR, DHR38 requires coactivation of its heterodimer partner in order to be competent to respond to ecdysteroids. The structure of the “ligand binding-domain” of DHR38 revealed the lack of well-defined ligand-binding and conventional coactivator binding sites, explaining why no such interactions were detected in biochemical assays. Although both EcR and DHR38 require heterodimerization with USP to be ecdysteroid-responsive, these receptors appear to use alternate mechanisms for transactivation of gene expression.—LDC

Cell 10.1016/S0092867403004203 (2003).

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