Abstract

There is a growing awareness that nuclear compartmentation is an essential component of nuclear metabolism. This proposal is aimed at studying the estrogen receptor as a model to understand how nuclear comparmentation affects transcriptional activity. To achieve this goal, the subnuclear domains targeted by ER under varying hormonal conditions will studied using high resolution microscopy and colocalization studies with other markers of specific subnuclear domains. The regions within the estrogen receptor responsible for interaction with the nuclear matrix will be analyzed by the generation of deletion constructs and chimeric proteins. Finally, the interaction of ER with transcriptional coactivators and regressors will be analyzed in a nucleoskeletal context to determine how subnuclear compartmentation of these factors regulates gene transcription.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK009787-02
Application #
2900110
Study Section
Special Emphasis Panel (ZRG2-END (01))
Program Officer
Hyde, James F
Project Start
1999-03-16
Project End
Budget Start
1999-03-16
Budget End
2000-03-15
Support Year
2
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

Sharp, Z Dave; Stenoien, David L; Mancini, Maureen G et al. (2004) Inactivating Pit-1 mutations alter subnuclear dynamics suggesting a protein misfolding and nuclear stress response. J Cell Biochem 92:664-78
Nye, Anne C; Rajendran, Ramji R; Stenoien, David L et al. (2002) Alteration of large-scale chromatin structure by estrogen receptor. Mol Cell Biol 22:3437-49
Stenoien, D L; Nye, A C; Mancini, M G et al. (2001) Ligand-mediated assembly and real-time cellular dynamics of estrogen receptor alpha-coactivator complexes in living cells. Mol Cell Biol 21:4404-12
Stenoien, D L; Patel, K; Mancini, M G et al. (2001) FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nat Cell Biol 3:15-23
Stenoien, D L; Simeoni, S; Sharp, Z D et al. (2000) Subnuclear dynamics and transcription factor function. J Cell Biochem Suppl Suppl 35:99-106
Stenoien, D L; Mancini, M G; Patel, K et al. (2000) Subnuclear trafficking of estrogen receptor-alpha and steroid receptor coactivator-1. Mol Endocrinol 14:518-34
Stenoien, D L; Cummings, C J; Adams, H P et al. (1999) Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum Mol Genet 8:731-41