Steroid hormones exert their effects on cells via the target genes. This regulation may be primary or secondary. Secondary is characterized by the requirement for ongoing protein synthesis regulation of transcription of specific glucocorticoid response to effect the induction of transcription. Little is known about the underlying molecular mechanisms or the transcription factors which are required for secondary response.
The specific aims of this grant directly address this question.
SPECIFIC AIM 1 : To characterize more fully the DNA sequences required for the secondary glucocorticoid response of the rat alpha2u globulin gene family.
SPECIFIC AIM 2 : To transfer secondary glucocorticoid inducibility of an alpha2u globulin gene into cells in which this gene is not hormone-inducible.
SPECIFIC AIM 3 : To analyze the early events in the secondary glucocorticoid induction of alpha2u globulin to determine if induction is preceded by a transient repression of transcription mediated by the glucocorticoid receptor.
SPECIFIC AIM 4 : To analyze a cDNA which has been cloned from an expression library which encodes a helix-turn-helix transcription factor which binds to control elements in the alpha2u globulin gene which are required for secondary glucocorticoid induction. Aberrant expression or expression of mutant forms of transcription factors have been linked to specific disease states. An understanding of the normal regulation of the activity of transcription factors is crucial for the understanding of the mechanisms which may lead to aberrant expression of these proteins.
|Slomiany, B A; D'Arigo, K L; Kelly, M M et al. (2000) C/EBPalpha inhibits cell growth via direct repression of E2F-DP-mediated transcription. Mol Cell Biol 20:5986-97|
|Slomiany, B A; Kelly, M M; Kurtz, D T (2000) Extraction of nuclear proteins with increased DNA binding activity. Biotechniques 28:938-42|
|Schwartz, D A; Kurtz, D T (1996) Sequence requirements for secondary glucocorticoid inducibility of rat alpha 2u globulin genes. Mol Cell Endocrinol 120:153-9|