THE EMERGING ROLE OF TPR-DOMAIN IMMUNOPHILINS IN THE MECHANISM OF ACTION OF STEROID RECEPTORS

GISELA I. MAZAIRA; MARIANA LAGADARI; ALEJANDRA G. ERLEJMAN; MARIO D. GALIGNIANA

NUCLEAR RECEPTORS RESEARCH

Agial Publishing Group

Año: 2014 vol. 1

2314-5706

In the absence of ligand, some members of nuclear receptor family such as corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus upon steroid-binding. Other members of the family such as the estrogen receptor are constitutively nuclear. Regardless of their primary location, these oligomeric proteins undergo a dynamic nuclear-cytoplasmic shuttling that has always been assumed to occur in a stochastic manner by simple diffusion. Although heuristic, this oversimplified model has never beendemonstrated. Moreover, it has always been assumed that the first step related to receptor activation is the dissociation of the Hsp90-based heterocomplex, a process referred to as transformation. Nonetheless, recent experimental evidence indicates that the chaperone machinery is required for the retrotransport of the receptor throughout the cytoplasm and facilitates its passage through the nuclear pore. Therefore, transformation is actually a nuclear event. A group of Hsp90-binding co-chaperones belonging to the immunophilin family plays a cardinal role not only in that mechanism for receptor movement, but also in nuclear events leading to interactions with nuclear sites of action and the regulation of transcriptional activity. In this article we analyze the importance of molecular chaperones and co-chaperones in the molecular mechanism of action of steroid receptors.