Abstract

The specific aims include: 1) Test the role of SLB, a putative new co-activator in the regulation of prolactin transcription. 2) Evaluate the functional significance of the interaction of Pit-1 with CBP through the use of a genetic screen to identify mutations in the Pit-1 POU domain which disrupt bindind to CBP. 3) Determine if the cAMP and TRH signaling pathways lead to changes in the chromatin structure of the PRL gene. 4) Determine if stimulation of prolactin transcription involves changes in the recruitment of transcriptional co-activators or co-repressors and changes in histone modification. 5) Test the role that specific transcription factors, co-activators and co-repressors play in organizing the chromatin structure and transcriptional potential of the prolactin gene. This will involve chromatin reconstitution using an in vivo Xenopus oocyte system as well in vitro using a Drosophila embryo 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 #
5R01DK040339-15
Application #
6624858
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Malozowski, Saul N
Project Start
1988-09-20
Project End
2005-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
15
Fiscal Year
2003
Total Cost
$302,000
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Howard, Paul W; Jue, Shall F; Maurer, Richard A (2009) Expression of the synaptotagmin I gene is enhanced by binding of the pituitary-specific transcription factor, POU1F1. Mol Endocrinol 23:1563-71
Kievit, Paul; Maurer, Richard A (2005) The pituitary-specific transcription factor, Pit-1, can direct changes in the chromatin structure of the prolactin promoter. Mol Endocrinol 19:138-47
Kievit, P; Lauten, J D; Maurer, R A (2001) Analysis of the role of the mitogen-activated protein kinase in mediating cyclic-adenosine 3',5'-monophosphate effects on prolactin promoter activity. Mol Endocrinol 15:614-24
Howard, P W; Maurer, R A (2001) A point mutation in the LIM domain of Lhx3 reduces activation of the glycoprotein hormone alpha-subunit promoter. J Biol Chem 276:19020-6
Howard, P W; Maurer, R A (2000) Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors. J Biol Chem 275:13336-42
Wang, Y H; Jue, S F; Maurer, R A (2000) Thyrotropin-releasing hormone stimulates phosphorylation of the epidermal growth factor receptor in GH3 pituitary cells. Mol Endocrinol 14:1328-37
Wang, Y H; Maurer, R A (1999) A role for the mitogen-activated protein kinase in mediating the ability of thyrotropin-releasing hormone to stimulate the prolactin promoter. Mol Endocrinol 13:1094-104
Nowakowski, B E; Okimura, Y; Maurer, R A (1997) Characterization of DNA regions mediating the ability of Ca2+/calmodulin dependent protein kinase II to stimulate prolactin promoter activity. Mol Cell Endocrinol 132:109-16
Liang, J; Moye-Rowley, S; Maurer, R A (1995) In vivo mutational analysis of the DNA binding domain of the tissue-specific transcription factor, Pit-1. J Biol Chem 270:25520-5
Howard, P W; Maurer, R A (1995) A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways. J Biol Chem 270:20930-6

Showing the most recent 10 out of 21 publications