Abstract

This project will investigate how steroid receptors interact with the transcription machinery to activate transcription of specific genes. An 810 amino acid fragment of a recently identified protein called GRIP1 interacts with the hormone binding domain of steroid receptors in an agonist dependent manner. In yeast, GRIP1 serves as a transcriptional coactivator for steroid receptors by interacting with the AF2 transcriptional activation domain of steroid receptors. Characterization of GRIP1 will be continued by first completing the cloning and sequencing of the coding region. The possibility that GRIP1 may interact with other nuclear receptors will be investigated. The functional domains of GRIP1 will be mapped as well as the specific subregions of the steroid receptors that GRIP1 interacts with. Cell and tissue specificity of GRIP1 expression will be determined. The ability of GRIP1 to interact with and serve as a coactivator for steroid receptors in mammalian cells will be examined. Finally, the mechanism of transcriptional coactivation by GRIP1 will be studied by looking for interactions between GRIP1 and known components of the transcription machinery, as well as by initiating studies with an in vitro transcription system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043093-10
Application #
6329356
Study Section
Endocrinology Study Section (END)
Program Officer
Margolis, Ronald N
Project Start
1990-07-01
Project End
2001-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
10
Fiscal Year
2001
Total Cost
$269,204
Indirect Cost

  Institution

Name
University of Southern California
Department
Pathology
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

Jin, Ming Li; Kim, Young Woong; Jin, Hong Lan et al. (2018) Aberrant expression of SETD1A promotes survival and migration of estrogen receptor ?-positive breast cancer cells. Int J Cancer 143:2871-2883
Poulard, Coralie; Baulu, Estelle; Lee, Brian H et al. (2018) Increasing G9a automethylation sensitizes B acute lymphoblastic leukemia cells to glucocorticoid-induced death. Cell Death Dis 9:1038
Lee, Brian H; Stallcup, Michael R (2018) Different chromatin and DNA sequence characteristics define glucocorticoid receptor binding sites that are blocked or not blocked by coregulator Hic-5. PLoS One 13:e0196965
Lee, Brian H; Stallcup, Michael R (2017) Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes. J Biol Chem 292:9320-9334
Yu, E J; Kim, S-H; Kim, H J et al. (2016) Positive regulation of ?-catenin-PROX1 signaling axis by DBC1 in colon cancer progression. Oncogene 35:3410-8
Chodankar, Rajas; Wu, Dai-Ying; Gerke, Daniel S et al. (2015) Selective coregulator function and restriction of steroid receptor chromatin occupancy by Hic-5. Mol Endocrinol 29:716-29
Wu, Dai-Ying; Bittencourt, Danielle; Stallcup, Michael R et al. (2015) Identifying differential transcription factor binding in ChIP-seq. Front Genet 6:169
Chodankar, Rajas; Wu, Dai-Ying; Schiller, Benjamin J et al. (2014) Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a gene-selective manner. Proc Natl Acad Sci U S A 111:4007-12
Liu, Xingxing; Giguère, Vincent (2014) Inactivation of RAR? inhibits Wnt1-induced mammary tumorigenesis by suppressing epithelial-mesenchymal transitions. Nucl Recept Signal 12:e004
Jeong, Kwang Won; Andreu-Vieyra, Claudia; You, Jueng Soo et al. (2014) Establishment of active chromatin structure at enhancer elements by mixed-lineage leukemia 1 to initiate estrogen-dependent gene expression. Nucleic Acids Res 42:2245-56

Showing the most recent 10 out of 64 publications