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, usp3 and usp4, 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, usp2, 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.

The Atomic Bomb Casualty Commission in retrospect

For 50 years, the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF), have conducted epidemiological and genetic studies of the survivors of the atomic bombs and of their children. This research program has provided the primary basis for radiation health standards. Both ABCC (1947–1975) and RERF (1975 to date) have been a joint enterprise of the United States (through the National Academy of Sciences) and of Japan. ABCC began in devastated, occupied Japan. Its mission had to be defined and refined. Early research revealed the urgent need for long term study. In 1946, a Directive of President Truman enjoined the National Research Council of the National Academy of Sciences to develop the program. By 1950, ABCC staff exceeded 1,000, and clinical and genetic studies were underway. Budgetary difficulties and other problems almost forced closure in 1953. In 1955, the Francis Report led to a unified epidemiological study. Much progress was made in the next decade, but changing times required founding of a binational nonprofit organization (RERF) with equal participation by Japan and the United States. New programs have been developed and existing ones have been extended in what is the longest continuing health survey ever undertaken.