Abstract

The overall hypothesis of this Program Project Grant proposal is that in the process of regulating nuclear receptor (NR) activity, individual members of the steroid receptor coactivator (SRC) family coordinate the expression of subsets of NR target genes in a ligand and tissue-specific manner. This project will identify the role that specific SRC family members play in the regulation of a differential tissue response to specific steroid hormone responsive to estrogen, progesterone, and androgens, and to elucidate the effect of ablation of SRC-1, SRC-2/TIF-2, and SRC-3 on individual tissue transcriptional responses to these hormones. This will be accomplished in four Specific Aims:
Specific Aim 1 will expression.
Specific Aim 2 will investigate the involvement of SRC family members in the determine the participation of SRC family members in the regulation of mammary gland contribution to SRC family members to the regulation of uterine gene expression in response to progesterone and estrogen. The accomplishment of these Aims will facilitate the determination of the metabolic fingerprint of SRC function in the hormonal regulation of tissue physiology.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK059820-01
Application #
6416625
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

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

  Publications

Dasgupta, Subhamoy; Rajapakshe, Kimal; Zhu, Bokai et al. (2018) Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer. Nature 556:249-254
Rohira, Aarti D; Yan, Fei; Wang, Lei et al. (2017) Targeting SRC Coactivators Blocks the Tumor-Initiating Capacity of Cancer Stem-like Cells. Cancer Res 77:4293-4304
Zhao, Fei; Franco, Heather L; Rodriguez, Karina F et al. (2017) Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science 357:717-720
Xu, Yong; O'Malley, Bert W; Elmquist, Joel K (2017) Brain nuclear receptors and body weight regulation. J Clin Invest 127:1172-1180
Xu, Y; Qin, L; Sun, T et al. (2017) Twist1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression. Oncogene 36:1157-1166
Xie, Xin; Wu, San-Pin; Tsai, Ming-Jer et al. (2017) The Role of COUP-TFII in Striated Muscle Development and Disease. Curr Top Dev Biol 125:375-403
Yi, Ping; Wang, Zhao; Feng, Qin et al. (2017) Structural and Functional Impacts of ER Coactivator Sequential Recruitment. Mol Cell 67:733-743.e4
Lee, Hui-Ju; Kao, Chung-Yang; Lin, Shih-Chieh et al. (2017) Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development. Sci Rep 7:3136
Xie, Xin; Tsai, Sophia Y; Tsai, Ming-Jer (2016) COUP-TFII regulates satellite cell function and muscular dystrophy. J Clin Invest 126:3929-3941
Vasquez, Yasmin M; Wu, San-Pin; Anderson, Matthew L et al. (2016) Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis. Mol Endocrinol 30:518-32

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