The androgen receptor is a member of the nuclear receptor superfamily and functions as a ligand dependent transcription factor, mediates male sexual development, prostate development in the adult, and in abnormal situations influences primary prostatic cancer growth. The transcriptional activity of AR is affected by coregulators that influence a number of functional properties of AR, including ligand selectivity and DNA binding capacity. The goal of this project is to assess the extent to which inflammatory molecules influence androgen receptor ligand activity through interactions with nuclear receptor coregulators.
Specific aim 1 will examine whether a nuclear corepressor complex is required for antagonist function on androgen receptors and specific aim 2 will explore whether inflammatory molecules influence the function of the antagonist function through interactions with the corepressor complex.
Specific aim 3 will explore the specific mechanisms by which the coregulators influence AR ligand activity. The information gained from this research will be valuable in understanding the mechanisms by which aberrant coregulator activity or altered expression levels may be a contributing factor in the progression of diseases related to androgen receptor activity.
