Biological Actions of the Hsp90-binding Immunophilins FKBP51 and FKBP52

ZGAJNAR, NADIA R.; ERLEJMAN, ALEJANDRA G.; DE LEO, SONIA A.; PILIPUK, GRACIELA PIWIEN; LOTUFO, CECILIA M.; GALIGNIANA, MARIO D.

BIOMOLECULES

MDPI

Año: 2019 vol. 9

2218-273X

Immunophilins are a family of proteins whose signature domain is the peptidylprolylisomerasedomain. High molecular weight immunophilins are characterized by the additionalpresence of tetratricopeptide-repeats (TPR) through which they bind to the 90-kDa heat-shockprotein (Hsp90), and via this chaperone, immunophilins contribute to the regulation of thebiological functions of several client-proteins. Among these Hsp90-binding immunophilins, thereare two highly homologous members named FKBP51 and FKBP52 (FK506-binding protein of 51-kDa and 52-kDa, respectively) that were first characterized as components of the Hsp90-basedheterocomplex associated to steroid receptors. Afterwards, they emerged as likely contributors to avariety of other hormone-dependent diseases, stress-related pathologies, psychiatric disorders,cancer, and other syndromes characterized by misfolded proteins. The differential biological actionsof these immunophilins have been assigned to the structurally similar, but functionally divergentenzymatic domain. Nonetheless, they also require the complementary input of the TPR domain,most likely due to their dependence with the association to Hsp90 as a functional unit. FKBP51 andFKBP52 regulate a variety of biological processes such as steroid receptor action, transcriptionalactivity, protein conformation, protein trafficking, cell differentiation, apoptosis, cancerprogression, telomerase activity, cytoskeleton architecture, etc. In this article we discuss the biologyof these events and some mechanistic aspects.