Sc. Nair et al., MOLECULAR-CLONING OF HUMAN FKBP51 AND COMPARISONS OF IMMUNOPHILIN INTERACTIONS WITH HSP90 AND PROGESTERONE-RECEPTOR, Molecular and cellular biology, 17(2), 1997, pp. 594-603
A cDNA for human FKBP51 has been cloned and sequenced, and protein pro
ducts have been expressed in both in vitro and bacterial systems. The
deduced amino acid sequence for human FKBP51 is 90% identical to seque
nces of recently described murine proteins and is 55% identical to the
sequence of human FKBP52. Human FKBP51 mRNA is expressed in a wide ra
nge of tissues, and the protein has peptidylprolyl isomerase activity
that is inhibited by FK506 but not cyclosporine. FKBP51 is the same as
a previously described progesterone receptor-associated immunophilin
that, similar to FKBP52 and cyclophilin 40, is an Hsp90-binding protei
n and appears in functionally mature steroid receptor complexes along
with Hsp90 and p23. Each of the three receptor-associated immunophilin
s displays interactions with progesterone receptor that are more dynam
ic than Hsp90-receptor interactions. Whereas FKBP52 and FKBP51 compete
about equally well for binding to Hsp90 in a purified system, FKBP51
accumulates preferentially in progesterone receptor complexes assemble
d in a cell-free system. This observation provides a precedent for dif
ferential interactions between Hsp90-associated immunophilins and targ
et proteins such as steroid receptors.