Chaperone functions of the heat shock proteins associated with steroid receptors

Abstract

Mammalian steroid receptors exist in hormone-free cells in a heterocomplex that contains the three heat shock proteins hsp90, hsp70 and hsp56. Some protein kinases, including pp60 v-src and v-Raf, exist in similar cytosolic heterocomplexes containing hsp90 and a 50 kDa protein of unknown function, pp50. The four proteins—hsp90, hsp70, hsp56 and pp50—exist together in a heterocomplex independent of the presence of steroid receptors and protein kinases. Both the receptor and the protein kinase hetorocomplexes can be formed by a protein folding-heterocomplex assembly system in reticulocyte lysate that carries out an hsp70-dependent attachment of the proteins to the preformed heat shock protein complex. Association of receptors with this structure occurs at the termination of receptor translation and is critical for maintenance of the receptors in a transcriptionally inactive state in the absence of hormone. We discuss how this preformed protein folding structure may be involved in the subsequent targeted trafficking of steroid receptors through the cytoplasmic space to the nucleus.