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 protein 56 (hsp56)] and heat shock proteins 90 and 70 (hsp90 and hsp70) associate with steroid receptors and are believed to maintain the receptors in an inactive state. Recently, we showed that p59 purified from human lymphocytes is an immunophilin (FKBP59) which binds both FK506 and rapamycin. It was also demonstrated that immunosuppressant-FKBP59 complexes 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 rabbit uterine p59 also binds FK506 and rapamycin and that p59 or its homologue is associated with nontransformed progesterone receptors of rabbit uterus and chicken oviduct. This suggests that the immunophilin-heat shock protein-steroid receptor interaction is ubiquitous and not limited 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 addition, we found that the FKBP59-hsp complexes are more complicated than previously thought, involving other proteins such as actin and a 63-kDa protein, p63. The association of p63 to the p59 complex was inhibited by FK506 and rapamycin, suggesting that p63 could be a potential target for the immunosuppressive actions of these two drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Tai
P K
PK
Department of Obstetrics and Gynecology, Medical College of Ohio, Toledo 43699.
Chang
H
H
Albers
M W
MW
Schreiber
S L
SL
Toft
D O
DO
Faber
L E
LE
D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000378:metabolism; D010057:Oviducts / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D011987:Receptors, Steroid / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; D014599:Uterus / Q000378:metabolism
D000199:Actins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011987:Receptors, Steroid; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus