Abstract

This application has six goals. The first is to overproduce T3Rs in mammalian cells and develop methods for their purification. The second is to characterize the biochemical properties of the receptors, including their specific affinities for each other, for T3, and for various DNA binding sites. The third is to characterize the in vivo regulatory properties of the various T3R types using a recently developed quantitative transfection system. The fourth is to characterize the interactions between the ligand binding domains of the T3Rs genetically. The fifth is to use the purified receptors to develop in vitro transcription systems responsive to both their negative or positive regulatory effects. The sixth is to investigate the interactions of the purified receptors with other proteins of the nuclear hormone receptor superfamily.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043382-03
Application #
3244776
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1991-08-01
Project End
1994-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Pissios, P; Tzameli, I; Kushner, P et al. (2000) Dynamic stabilization of nuclear receptor ligand binding domains by hormone or corepressor binding. Mol Cell 6:245-53
Koh, Y S; Moore, D D (1999) Linkage of the nuclear hormone receptor genes NR1D2, THRB, and RARB: evidence for an ancient, large-scale duplication. Genomics 57:289-92
Na, S Y; Kim, H J; Lee, S K et al. (1998) IkappaBbeta interacts with the retinoid X receptor and inhibits retinoid-dependent transactivation in lipopolysaccharide-treated cells. J Biol Chem 273:3212-5
Seol, W; Chung, M; Moore, D D (1997) Novel receptor interaction and repression domains in the orphan receptor SHP. Mol Cell Biol 17:7126-31
Martinez, E; Moore, D D; Keller, E et al. (1997) The Nuclear Receptor Resource Project. Nucleic Acids Res 25:163-5
Zuo, F; Kraus, R J; Gulick, T et al. (1997) Direct modulation of simian virus 40 late gene expression by thyroid hormone and its receptor. J Virol 71:427-36
Seol, W; Mahon, M J; Lee, Y K et al. (1996) Two receptor interacting domains in the nuclear hormone receptor corepressor RIP13/N-CoR. Mol Endocrinol 10:1646-55
Lee, J W; Choi, H S; Gyuris, J et al. (1995) Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Mol Endocrinol 9:243-54
Seol, W; Choi, H S; Moore, D D (1995) Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Mol Endocrinol 9:72-85
Gulick, T; Cresci, S; Caira, T et al. (1994) The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci U S A 91:11012-6

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