The intersection of steroid receptors with molecular chaperones: Observations and questions

An involvement of molecular chaperones in the action and well-being of steroid receptors was recognized early in the molecular era of hormone research. However, this has continued to be a topic of much enquiry and some confusion. All steroid receptors associate with heat shock protein 90, the main character of a series of multiprotein chaperone complexes generally referred to as the heat shock protein 90 chaperoning machine. Receptor association with chaperones occurs in an ordered, step-wise fashion and is necessary for the maintenance of unliganded receptor in a state ready bind and respond to hormone. Chaperones additionally modulate how receptors respond to hormone and activate target genes. Although much is known about the participants in this chaperoning process and the consequences of chaperoning, many key questions remain unanswered, particularly those concerning molecular mechanisms, cellular dynamics, and the functions of an array of cochaperone proteins. Here, we point out several areas in need of investigation to encourage new ideas and participants in this burgeoning field.