Control of steroid receptor function and cytoplasmic-nuclear transport by heat shock proteins.
As targeted proteins that move within the cell, the steroid receptors have become very useful probes for understanding the linked phenomena of protein folding and transport. From the study of steroid receptor-associated proteins it has become clear over the past two years that these receptors are bound to a multiprotein complex containing at least two heat shock proteins, hsp90 and hsp56. Attachment of receptors to this complex in a cell-free system appears to require the protein unfolding/folding activity of a third heat shock protein, hsp70. Like the oncogenic tyrosine kinase pp60src, steroid receptors bind to this complex of chaperone proteins at the time of their translation. Binding of the receptor to the hsp90 component of the system occurs through the hormone binding domain and is under strict hormonal control. The hormone binding domain of the receptor acts as a transferable regulatory unit that confers both tight hormonal control and hsp90 binding onto chimaeric proteins. The model of folding and transport being developed for steroid receptors leads to some general suggestions regarding the folding and transport of targeted proteins in the cell.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
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Pratt
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D011987:Receptors, Steroid / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D011506:Proteins; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D004247:DNA; D022021:Tacrolimus Binding Proteins