CONICET | Buscador de Institutos y Recursos Humanos

Several nuclear factors such as p53 and steroid receptors (SRs) are assembled into heterocomplexes with hsp90, hsp70, p23 and a co-chaperone that possesses tetratricopeptide repeat domains (TPR). FKBP51 and FKBP52 are highly homologous TPR proteins belonging to the high molecular weight immunophilin (IMM) family. Both TPR proteins are abundant and highly ubiquitous; however, the biological function of these IMMs remains unknown. In previous works, we demonstrated that retrograde movement of those nuclear factors occurs on cytoskeletal tracks and depends on the association of hsp90FKBP52 with the dynein/dynactin motor complex. In this work we analyze the possible nuclear role of IMMs on the hormone-activated SR model. Ligand binding to SRs promoted the displacement of FKBP51 from the receptor complex and the subsequent recruitment of the IMM-like Ser/Thr-phosphatase PP5, FKBP52 and dynein. This complex favoured SR nuclear localization. Confocal microscopy imaging showed that FKBP52 colocalized with the SR in specific nuclear foci that also included the nuclear matrix-associated protein, NuMA. FKBP52 copurified with the nucleoskeleton and the glucocorticoid receptor (GR). Hsp90 and p23 were also recruited to the same nuclear domains. FKBP52 was also detected in transcriptionally active GR complexes containing components of the transcription machinery such as active RNA-polymerase II and SC35 factor. On the other hand, FKBP51 may colocalize or not with the receptor according to the nature of the bound hormone. Transcriptional assays demonstrated that FKBP51 exerts an inhibitory effect on the hormone-dependent transacriptional activity of SRs. In agreement with this observation, overexpressing FKBP51 favoured the nuclear colocalization with the nuclear factor.