P59 (FK506 BINDING PROTEIN-59) INTERACTION WITH HEAT-SHOCK PROTEINS IS HIGHLY CONSERVED AND MAY INVOLVE PROTEINS OTHER THAN STEROID-RECEPTORS

P59 [also known as FK506 binding protein 59 (FKBP59) or heat shock pro tein 56 (hsp56)] and heat shock proteins 90 and 70 (hsp90 and hsp70) a ssociate with steroid receptors and are believed to maintain the recep tors in an inactive state. Recently, we showed that p59 purified from human lymphocytes is an immunophilin (FKBP59) which binds both FK506 a nd rapamycin. It was also demonstrated that immunosuppressant-FKBP59 c omplexes associate with hsp90, hsp70, and the glucocorticoid receptor [Tai, P.-K. K., Albers, M. W., Chang, H., Faber, L. E., & Schreiber, S . L. (1992) Science 256, 1315-1318]. Here we provide evidence that rab bit uterine p59 also binds FK506 and rapamycin and that p59 or its hom ologue is associated with nontransformed progesterone receptors of rab bit uterus and chicken oviduct. This suggests that the immunophilin-he at shock protein-steroid receptor interaction is ubiquitous and not li mited to immune systems. A FKBP59 homologue complexed with hsp90-hsp70 was also detected in yeast, which suggests that the immunophilin-heat shock protein association has been evolutionarily conserved. In addit ion, we found that the FKBP59-hsp complexes are more complicated than previously thought, involving other proteins such as actin and a 63-kD a protein, p63. The association of p63 to the p59 complex was inhibite d by FK506 and rapamycin, suggesting that p63 could be a potential tar get for the immunosuppressive actions of these two drugs. Since both i mmunophilin and heat shock proteins have been suggested to be responsi ble for protein folding and assembly of new synthesized polypeptides, it is reasonable to propose that p59, in association with hsp70 and hs p90, forms the core structure of a universal molecular chaperone. This chaperone complex may be responsible for recognition, folding, assemb ly, and disassembly of steroid receptors or other regulatory proteins at or near the end of translation.