Abstract

The objective of this study is to dissect a mechanism of gene regulation by Steroidogenic Factor 1 (SF-1). The underlying hypothesis is that SF-1 functions as a mediator of discrete activation domains which are modulated by specific cofactors or coactivators. In order to test this hypothesis, the investigators will conduct a detailed structural functional analysis of SF-1. They will attempt to identify putative activation domains of SF-1, examine the activation capacity in the context of heterologous proteins, and determine their independent function in steroidogenic as well as nonsteroidogenic cell lines. Further studies will examine whether transcriptional activation by SF-1 requires interaction of its activation domain with cofactors. These cofactors will be identified using a yeast two-hybrid system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD034110-02
Application #
2634965
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Vachharajani, Akshaya; Bethin, Kathleen; Mouillet, Jean-Francois et al. (2006) The rare occurrence of absent adrenals in a term infant: a case report and review of the literature. Am J Perinatol 23:111-4
Yan, Xiaomei; Mouillet, Jean-Francois; Ou, Qinglin et al. (2003) A novel domain within the DEAD-box protein DP103 is essential for transcriptional repression and helicase activity. Mol Cell Biol 23:414-23
Ou, Q; Mouillet, J F; Yan, X et al. (2001) The DEAD box protein DP103 is a regulator of steroidogenic factor-1. Mol Endocrinol 15:69-79
Sadovsky, Y; Dorn, C (2000) Function of steroidogenic factor 1 during development and differentiation of the reproductive system. Rev Reprod 5:136-42
Crawford, P A; Dorn, C; Sadovsky, Y et al. (1998) Nuclear receptor DAX-1 recruits nuclear receptor corepressor N-CoR to steroidogenic factor 1. Mol Cell Biol 18:2949-56
Sadovsky, Y; Crawford, P A (1998) Developmental and physiologic roles of the nuclear receptor steroidogenic factor-1 in the reproductive system. J Soc Gynecol Investig 5:6-12
Crawford, P A; Polish, J A; Ganpule, G et al. (1997) The activation function-2 hexamer of steroidogenic factor-1 is required, but not sufficient for potentiation by SRC-1. Mol Endocrinol 11:1626-35