Abstract

The hypothesis of this proposal is that the lactotrope-specific and Ras-regulated expression of PRL is governed by the selective Ets-1/Pit-1 protein partnership, which in turn is dictated by a specific protein- protein interaction domain and organization of binding sites in the composite RRE. The four specific aims are to: 1) map the precise amino acids of Ets-1 and Pit-1 required for their functional and physical interaction; 2) define the distance and orientation requirements for the two protein binding sites in the composite elements; 3) identify the Ets factors in GH4 cells that specifically recognize the Ets site in the RRE; and 4) elucidate the role of Ets factors in endogenous PRL gene expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046868-09
Application #
6517272
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Blondel, Olivier
Project Start
1994-06-01
Project End
2003-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
9
Fiscal Year
2002
Total Cost
$265,970
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Roof, Allyson K; Trudeau, Tammy; Gutierrez-Hartmann, Arthur (2018) Pituitary somatolactotropes evade an oncogenic response to Ras. Mol Cell Endocrinol 476:165-172
Roof, Allyson K; Jirawatnotai, Siwanon; Trudeau, Tammy et al. (2018) The Balance of PI3K and ERK Signaling Is Dysregulated in Prolactinoma and Modulated by Dopamine. Endocrinology 159:2421-2434
Booth, Allyson; Trudeau, Tammy; Gomez, Crystal et al. (2014) Persistent ERK/MAPK activation promotes lactotrope differentiation and diminishes tumorigenic phenotype. Mol Endocrinol 28:1999-2011
Jean, Annie; Gutierrez-Hartmann, Arthur; Duval, Dawn L (2010) A Pit-1 threonine 220 phosphomimic reduces binding to monomeric DNA sites to inhibit Ras and estrogen stimulation of the prolactin gene promoter. Mol Endocrinol 24:91-103
Jedlicka, Paul; Sui, Xiaomei; Gutierrez-Hartmann, Arthur (2009) The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice. BMC Cancer 9:197
Jedlicka, Paul; Sui, Xiaomei; Sussel, Lori et al. (2009) Ets transcription factors control epithelial maturation and transit and crypt-villus morphogenesis in the mammalian intestine. Am J Pathol 174:1280-90
Gutierrez-Hartmann, Arthur; Duval, Dawn L; Bradford, Andrew P (2007) ETS transcription factors in endocrine systems. Trends Endocrinol Metab 18:150-8
Ferry, A L; Locasto, D M; Meszaros, L B et al. (2005) Pit-1beta reduces transcription and CREB-binding protein recruitment in a DNA context-dependent manner. J Endocrinol 185:173-85
Schweppe, Rebecca E; Melton, Alexis A; Brodsky, Kelley S et al. (2003) Purification and mass spectrometric identification of GA-binding protein (GABP) as the functional pituitary Ets factor binding to the basal transcription element of the prolactin promoter. J Biol Chem 278:16863-72
Duval, Dawn L; Jean, Annie; Gutierrez-Hartmann, Arthur (2003) Ras signaling and transcriptional synergy at a flexible Ets-1/Pit-1 composite DNA element is defined by the assembly of selective activation domains. J Biol Chem 278:39684-96

Showing the most recent 10 out of 22 publications