Molecular chaperones shape steroid receptor action and pharmacologic strategies

Chaperone oligomers exist in cell cytosols as preassembled heterocomplexes that function as protein-folding molecular machines able to assemble essential proteins related to families that embrace steroid receptors, protein-kinases, ubiquitin-ligases, and transcription factors, among other families of key proteins. Actually, steroid receptors may be considered a particular subset of transcription factors that can be activated by specific ligands. Some of them are primarily located in the cytoplasm, others are constitutively nuclear, but regardless of their subcellular distribution, they are constantly shuttling between both compartments in a highly dynamic manner. The chaperone heterocomplex associated to steroid receptors is not only involved in the stabilization of their conformation preventing their degradation by the proteasome, but it is also critical for the molecular mechanism of transport of these receptors and their subnuclear redistribution. In this article we summarized some of the general properties of molecular chaperones, in particular those belonging to a subfamily that is highly inducible by thermal shock, the heat-shock proteins, and review the most recent findings performed in the field of soluble protein trafficking, where molecular chaperones play a critical role.Fil: Mazaira, Gisela Ileana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Lagadari, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Elerjman, Alejandra G.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin