Molecular chaperone activity and biological regulatory actions of the TPR-domain immunophilins FKBP51 and FKBP52.
Immunophilins comprise a family of intracellular proteins with peptidyl-prolyl-(cis/trans)-isomerase activity. These foldases are abundant, ubiquitous, and able to bind immunosuppressant drugs, from which the term immunophilin derives. Family members are found in abundance in virtually all organisms and subcellular compartments, and their amino acid sequences are conserved phylogenetically. Immunophilins possess the ability to function as molecular chaperones favoring the proper folding and biological regulation of their biological actions. Their ability to interact via their TPR domains with the 90-kDa heat-shock protein, and through this chaperone, with several signalling cascade factors is of particular importance. Among the family members, the highly homologous proteins FKBP51 and FKBP52 were first characterized due to their ability to interact with steroid hormone receptors. Since then, much progress has been made in understanding the mechanisms by which they regulate receptor signaling and the resulting roles they play not only in endocrine processes, but also in cell architecture, neurodifferentiation, and tumor progression. In this article we review the most relevant features of these two immunophilins and their potential as pharmacologic targets.
Alejandra G
AG
Erlejman
Mariana
M
Lagadari
Diondra C
DC
Harris
Marc B
MB
Cox
IBYME, Vuelta de Obligado 2490, Buenos Aires (C1428ADN), Argentina. mgali@qb.fcen.uba.ar.
Mario D
MD
Galigniana
D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
D018832:Molecular Chaperones; D011987:Receptors, Steroid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C403485:tacrolimus binding protein 4