Abstract

The function of thyroid hormone receptors (TRs) as ligand dependent transcription factors is mediated by their interaction with a variety of proteins. Over the previous funding period the major focus of this project was identification and characterization of TR interacting proteins (TRIPs) and more than 20 were identified. The focus of the current period is on the mechanism of action of a subset of these TR interactors in both chromatin and non-chromatin contexts. The first specific aim is to characterize in detail the biochemical basis of the strong stimulatory effect of TRIP7, a nucleosomal protein, on TR DNA binding, and to determine functional consequences of this effect. The second specific aim is to test the hypothesis that the SWI/SNF complex is involved in the chromatin remodeling associated with activation by the TRs and, more broadly, to characterize the functional role of the SWI/SNF complex in TR action.
The third aim i s to characterize the mechanism of action of the recently identified potential co-activator TRIP4 that does not appear to act at the chromatin level.
The final aim i s to continue to maintain and develop the Thyroid hormone Receptor Resource, a web-based source of information on the TRs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043382-09
Application #
2905432
Study Section
Endocrinology Study Section (END)
Program Officer
Margolis, Ronald N
Project Start
1991-08-01
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  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
Baes, M; Gulick, T; Choi, H S et al. (1994) A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 14:1544-52

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