2 FKBP-RELATED PROTEINS ARE ASSOCIATED WITH PROGESTERONE-RECEPTOR COMPLEXES

Unactivated steroid receptors are in heterooligomeric complexes that p erhaps stabilize a partially folded receptor polypeptide prior to horm one-dependent activation. Hsp90 is a common receptor component and hsp 70 is a component of progesterone receptors; both appear to be importa nt as general mediators of protein folding and assembly events. In add ition to hsp90, mammalian steroid receptor complexes contain a 52-59-k Da protein that is an FK506-binding immunophilin and has peptidyl-prol yl isomerase activity. Other receptor-associated proteins have been id entified but not well-characterized. In the present study, we obtained partial amino acid sequences for two avian progesterone receptor comp onents, p50 and p54. From sequence comparisons with known proteins, th ey appear to be distinct members of the FKBP family of immunophilins. Six p50 peptide sequences have 80% identity with regions of rabbit FKB P52; seven p54 peptide sequences have 60% identity with rabbit FKBP52. Interaction of p54 with receptor is distinct from p50 in that its bin ding in vitro is highly sensitive to progesterone or N-ethylmaleimide. An anti-p54 monoclonal antibody was developed that detects a 55-kDa p rotein in rabbit and human tissues; in a cell-free reconstitution syst em, the rabbit antigen binds to chicken progesterone receptor along wi th rFKBP52. While p50 appears to be the chicken homolog of FKBP52, p54 is perhaps a novel member of the FKBP family that, in addition to FKB P52, interacts with progesterone receptor.