Heat shock protein 90 and the nuclear transport of progesterone receptor

Steroid receptors exist as large oligomeric complexes in hypotonic cell ext racts. In the present work, we studied the nuclear transport of the 2 major components of the oligomeric complex, the receptor itself and the heat sho ck protein 90 (Hsp90), by using different in vitro transport systems: digit onin permeabilized cells and purified nuclei. We demonstrate that the stabi lized oligomeric complex of progesterone receptor (PR) cannot be transporte d into the nucleus and that unliganded PR salt dissociated from Hsp90 is tr ansported into the nucleus. When nonstabilized PR oligomer was introduced i nto the nuclear transport system, the complex dissociated and the PR but no t the Hsp90 was transported into the nucleus. If PR exists as an oligomeric form after synthesis, as suggested by the experiments with reticulocyte ly sate, the present results suggest that the complex is short-lived and is di ssociated before or during nuclear transport. Thus, the role of Hsp90 in PR action is likely to reside in the Hsp90-assisted chaperoning process of PR preceding nuclear transport of the receptor.