A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor.
A variety of regulatory proteins, including different classes of transcription factors and protein kinases, have been identified in complexes with Hsp90. On careful examination of unactivated progesterone receptor complexes, eight different protein participants have been identified, and each can be considered a component of the cytoplasmic molecular chaperone machinery. These proteins are Hsp90, Hsp70, Hip, p60, p23, FKBP51, FKBP52 and Cyp40. Studies in a cell-free assembly system have helped to define a highly ordered, dynamic pathway for assembly of progesterone receptor complexes. In the present study, target proteins other than progesterone receptor were used in this cell-free system to assemble complexes in vitro and to compare the composition of resulting complexes. Targets used were human estrogen receptor, human Fes protein-tyrosine kinase, human heat shock transcription factor Hsf1, and human aryl hydrocarbon receptor. The striking similarity of resulting target complexes with previously characterized progesterone receptor complexes suggest that each of these targets undergoes a common assembly pathway involving multiple chaperone components in addition to Hsp90.
Nair
S C
SC
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198, USA.
Toran
E J
EJ
Rimerman
R A
RA
Hjermstad
S
S
Smithgall
T E
TE
Smith
D F
DF
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D018411:Spodoptera / Q000166:cytology; D014157:Transcription Factors
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D011518:Proto-Oncogene Proteins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes