The objective of this study is to determine the role of immunophilins in the regulation of steroid receptor function. The proposed research will examine structure-function correlates in the immunophilins Cyp40, FKBP51, and FKBP52 in vitro; use a yeast genetic mutant lacking the homolog of Cyp40 to test for functional complementation by human immunophilins; and examine the function of immunophilins in mammalian cell lines expressing steroid receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK048218-07
Application #
6176504
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Margolis, Ronald N
Project Start
1994-05-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
7
Fiscal Year
2000
Total Cost
$243,402
Indirect Cost
Name
Mayo Clinic, Arizona
Department
Type
DUNS #
City
Scottsdale
State
AZ
Country
United States
Zip Code
85259
Cox, Marc B; Riggs, Daniel L; Hessling, Martin et al. (2007) FK506-binding protein 52 phosphorylation: a potential mechanism for regulating steroid hormone receptor activity. Mol Endocrinol 21:2956-67
Riggs, Daniel L; Cox, Marc B; Tardif, Heather L et al. (2007) Noncatalytic role of the FKBP52 peptidyl-prolyl isomerase domain in the regulation of steroid hormone signaling. Mol Cell Biol 27:8658-69
Tranguch, Susanne; Wang, Haibin; Daikoku, Takiko et al. (2007) FKBP52 deficiency-conferred uterine progesterone resistance is genetic background and pregnancy stage specific. J Clin Invest 117:1824-34
Tranguch, Susanne; Smith, David F; Dey, Sudhansu K (2006) Progesterone receptor requires a co-chaperone for signalling in uterine biology and implantation. Reprod Biomed Online 13:651-60
Denny, Wesley B; Prapapanich, Viravan; Smith, David F et al. (2005) Structure-function analysis of squirrel monkey FK506-binding protein 51, a potent inhibitor of glucocorticoid receptor activity. Endocrinology 146:3194-201
Daikoku, Takiko; Tranguch, Susanne; Friedman, David B et al. (2005) Proteomic analysis identifies immunophilin FK506 binding protein 4 (FKBP52) as a downstream target of Hoxa10 in the periimplantation mouse uterus. Mol Endocrinol 19:683-97
Riggs, Daniel L; Cox, Marc B; Cheung-Flynn, Joyce et al. (2004) Functional specificity of co-chaperone interactions with Hsp90 client proteins. Crit Rev Biochem Mol Biol 39:279-95
Nelson, Gregory M; Prapapanich, Viravan; Carrigan, Patricia E et al. (2004) The heat shock protein 70 cochaperone hip enhances functional maturation of glucocorticoid receptor. Mol Endocrinol 18:1620-30
Smith, David F (2004) Tetratricopeptide repeat cochaperones in steroid receptor complexes. Cell Stress Chaperones 9:109-21
Cheung-Flynn, Joyce; Roberts, Patricia J; Riggs, Daniel L et al. (2003) C-terminal sequences outside the tetratricopeptide repeat domain of FKBP51 and FKBP52 cause differential binding to Hsp90. J Biol Chem 278:17388-94

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