Molecular chaperone activity of TPR-domain immunophilins

ERLEJMAN AG; LAGADARI M; COX, M.B.; GALIGNIANA M.

CURRENT PROTEIN AND PEPTIDE SCIENCE

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2012

1389-2037

FKBP51 and FKBP52 are TPR-domain proteins belonging to a diverse family of regulators of steroid hormone receptor signaling, including receptor maturation, hormone binding and nuclear translocation. TPR-domain proteins are characterized for the presence of 34 amino acid repeats, those showing a peptidyl-prolyl isomerase domain being named TPR-immunophilins. Although structurally similar, they are functionally divergent, which is largely attributed to differences in the FK1 domain and the proline-rich loop. FKBP51 and FKBP52 are archetype factors of this family. They have emerged as likely contributors to a variety of hormone-dependent diseases, including stress-related diseases, immune function, reproductive functions and a variety of cancers. In addition, recent studies have implicated FKBP51 and FKBP52 in Alzheimer’s disease and other protein aggregation disorders. Both proteins are able to interact with 90-kDa heatshock protein Hsp90, and many of the biological actions of both immunophilins are close-related to such functional association. This article analyzes our current understanding of FKBP51 and FKBP52 interactions within the receptor–haperone complex, their contributions to health and disease, and their potential as therapeutic targets for the treatment of these diseases.