Sgtα: a novel independent regulator of steroid hormone receptors (567.8)

Abstract

Steroid hormone receptors (SHRs) are essential for the regulation of developmental, reproductive, and physiological homeostasis in eukaryotes. SHRs belong to the nuclear receptor superfamily, and comprise the androgen (AR), glucocorticoid (GR), progesterone (PR), mineralocorticoid (MR), and estrogen receptors (ER). Understanding the regulation of SHRs is critical for the development of novel therapeutic strategies for SHR‐mediated diseases. Heat shock protein (Hsp) 90/70 kDa assembly is essential for the dynamic chaperone complex that directs SHRs folding. A recently identified cochaperone, human small glutamine‐rich TPR‐containing protein alpha (SGTα), has been shown to negatively regulate AR by retaining AR in the cytoplasm. Using functional yeast and mammalian reporter assays, we have demonstrated that SGTα can also regulate GR and PR. Interestingly, when co‐expressed with immunophilin FKBP52, a positive regulator of the same receptors, SGTα continues to abrogate receptor activity. Another TPR‐containing protein present in yeast, CPR7, can positively regulate AR. Thus, we assessed the effects SGTα has in a yeast model system using a CPR7 deletion strain. We observed the same pattern seen with FKBP52, suggesting that the regulation by SGTα is not solely based on its TPR domain. Future studies aim to determine the role for SGTα at the transcriptional level.Grant Funding Source: Supported by the NIH/SCORE grant from the NIGMS (1SC1GM084863) and COURI