Roles for the 51-kDa and 52-kDa FK506-Binding Proteins (FKBP51 and FKBP52) in Signaling and Disease

C.L. STORER, C.A. DICKEY, M.D. GALIGNIANA, T. REIN, M.B. COX

TRENDS IN ENDOCRINOLOGY AND METABOLISM

ELSEVIER SCIENCE LONDON

Año: 2011 vol. 22 p. 481 - 490

1043-2760

The large FK506-binding proteins, FKBP51 and FKBP52, are diverse regulators of steroid hormone receptor signaling pathways including regulation of receptor maturation, hormone binding, and nuclear translocation. Although structurally similar, FKBP51 and FKBP52 are functionally divergent, which has been largely attributed to differences in the FK1 domain and the proline-rich loop within that domain. FKBP52 is a positive regulator of androgen, progesterone and glucocorticoid receptors, whereas FKBP51 is generally considered a negative regulator of these receptors. These differences are also reflected in the fkbp51 and fkbp52-deficient mice with fkbp52-deficient mice displaying phenotypes consistent with androgen, progesterone and glucocorticoid insensitivity syndromes and the fkbp51-deficient mice displaying no obvious morphological or physiological defects. As a result of their roles in receptor signaling pathways FKBP51 and FKBP52 have emerged as likely contributors to a variety of hormone-dependent processes and diseases including stress-related diseases that are linked to the hypothalamus pituitary adrenal axis, immune function, and a variety of cancers. In addition, recent studies have implicated FKBP51 and FKBP52 in Alzheimer’s disease and other protein aggregation disorders.