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 trans cription factors and protein kinases, have been identified in complexe s with Hsp90. On careful examination of unactivated progesterone recep tor complexes, eight different protein participants have been identifi ed, and each can be considered a component of the cytoplasmic molecula r 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 pr ogesterone receptor complexes. In the present study, target proteins o ther than progesterone receptor were used in this cell-free system to assemble complexes in vitro and to compare the composition of resultin g complexes. Targets used were human estrogen receptor, human Fes prot ein-tyrosine kinase, human heat shock transcription factor Hsf1, and h uman aryl hydrocarbon receptor. The striking similarity of resulting t arget complexes with previously characterized progesterone receptor co mplexes suggest that each of these targets undergoes a common assembly pathway involving multiple chaperone components in addition to Hsp90.