Steroid Receptors

Chaperones Prefer Experienced Receptors

Science's STKE  07 Mar 2000:
Vol. 2000, Issue 22, pp. tw7
DOI: 10.1126/stke.2000.22.tw7

Steroid hormone receptors are intracellular ligand-activated transcription factors. The activity of the steroid hormone receptors is also influenced by interactions with molecular chaperones, such as heat shock proteins (Hsp90, Hsp70, Hsp40), immunophilins, and p23. Freeman et al. found that mammalian p23, tsp23 (transcript similar p23), and the yeast homolog Sba1 had differential effects on steroid receptor-activated reporter gene activity in transfected mammalian cells and yeast, depending on the hormone and receptor expressed. The alteration in transcriptional activity caused by p23, tsp23, and Sba1 required several hours to develop, consistent with an interaction of p23 proteins with the hormone-bound holoreceptor. Anisotropy measurements suggested that p23 promoted the dissociation of the thyroid hormone receptor-DNA complex and inhibited the binding of thyroid receptor to DNA in vitro. The authors speculate that p23 proteins interact with a subset of "experienced" receptors that have engaged in binding the hormone response element; thus, these experienced receptors would gradually accumulate in cells chronically exposed to hormone, accounting for the slow kinetics of p23 action. The concept of experienced receptors is intriguing, especially in the context of the recent results on rapid exchange of the hormone-receptor complexes at DNA binding sites from McNally et al. that was highlighted in a TWIST.

Freeman, B.C., Felts, S.J., Toft, D.O., and Yamamoto, K.R. (2000) The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies. Genes Dev. 14: 422-434. [Abstract] [Full Text]

McNally, J.G., Müller, W.G., Walker, D., Wolford, R., and Hager, G.L. (2000) The glucocorticoid receptor: Rapid exchange with regulatory sites in living cells. Science 287: 1262-1265. [Abstract] [Full Text]