The hsp56 immunophilin component of steroid receptor heterocomplexes: could this be the elusive nuclear localization signal-binding protein?
In many cells, the glucocorticoid receptor undergoes rapid steroid-mediated translocation from the cytoplasm to the nucleus, and this receptor is an excellent model for studying the mechanism of targeted protein movement through the cytoplasm. For such unidirectional movement to occur, the receptor must attach to a retrograde movement system in a manner that involves the nuclear localization signal. It is improbable that such attachment occurs via a direct protein-protein interaction between the receptor and the movement system; rather, one or more linker proteins are likely to be involved. As with other steroid receptors, the glucocorticoid receptor is associated with several other proteins in a heterocomplex. Two of these receptor-associated proteins are the heat shock proteins hsp90 and hsp56, and a third heat shock protein, hsp70, is required for assembly of the receptor heterocomplex. The hormone binding domain of the steroid receptors determines the interaction with both hsp90 and hsp70. Hsp56 is known to bind to hsp90, but its potential site, or sites, of interaction with the receptor are undefined. Hsp56 has recently been cloned and demonstrated to be an immunophilin of the FK506/rapamycin binding class. The immunophilins have peptidyl-prolyl isomerase activity but their cellular functions are unknown. Herein, we review the literature on the hsp56 immunophilin component of the receptor heterocomplex and present a rationale for hsp56 being the protein that determines the direction of receptor movement via a direct protein-protein interaction with the nuclear localization signal.
Pratt
W B
WB
The Department of Pharmacology, The University of Michigan Medical School, Ann Arbor 48109-0626, USA.
Czar
M J
MJ
Stancato
L F
LF
Owens
J K
JK
D000818:Animals; D002467:Cell Nucleus / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D020104:Immunophilins / Q000502:physiology*; D008322:Mammals; D019913:Nuclear Localization Signals / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D022021:Tacrolimus Binding Proteins
D018841:HSP90 Heat-Shock Proteins; D019913:Nuclear Localization Signals; D011987:Receptors, Steroid; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins