This transport appears to occur along micotubular tracks. These data provide strong evidence that Hsp90 is an essential molecular chaperone for the nuclear transport of GRβ. Coimmunoprecipitation experiments verify that GRβ complexes with Hsp90 and the microtubule motor protein dynein.Ĭonclusions. 17-AAG, a specific Hsp90 inhibitor, completely blocks the nuclear accumulation of GRβ and consequently leads to the degradation of GRβ in proteasomes. Transfection with a GRβ expression construct produces an overexpression and accumulation of GRβ in the nucleus with a corresponding increase in nuclear Hsp90 amount. In normal and glaucomatous TM cells, the nuclear concentration of Hsp90 correlates with the nuclear expression of GRβ.

Coimmunoprecipitation was performed to study GRβ-Hsp90 complexes. The role of Hsp90 in GRβ transport and stability were determined with the Hsp90 inhibitor, 17-AAG and the proteasome inhibitor lactacystin. Immunocytochemistry and Western blot analysis were performed to detect the subcellular expression of GRβ and Hsp90 in normal and glaucomatous trabecular meshwork (TM) cells, as well as in TM cells overexpressing GRβ. In this study, the roles of Hsp90 in the nuclear transport of GRβ were investigated. The nuclear transport of the non–ligand-binding GRβ is still unknown. GRα undergoes steroid-dependent nuclear translocation by associating with a heat shock protein (Hsp)90 multiprotein heterocomplex. Glucocorticoid sensitivity in glaucoma has been attributed to differences in the expression of the two glucocorticoid receptors, GRα and GRβ.

Hsp90 a molecular chaperone