Figures & data
Figure 1. Model of Hsp90 and FKBP51 functions in adipogenesis. The adipogenic media contains insulin, 3-isobutyl-1-methylxanthine (IBMX), dexamethasone (DEXA), and is supplemented with fetal bovine serum that contains aldosterone (ALDO) among many other hormones. (A) Insulin activates many signaling pathways, among them Akt that phosphorylates GATA2 and FOXO-1 and -2, transcription factors that are excluded from the nucleus. (B) IBMX increases cAMP level leading to PKA activation that triggers the translocation of FKBP51 from mitochondria to the nucleus, possibly upon changes in its phosphorylation status. FKBP51 interacts with lamin B in the NL (nuclear lamina) modulating NL reorganization at the onset of adipogenesis. In addition, FKBP51 regulates GR-, MR- and PPARγ-target genes, and possibly other genes. (C) Upon DEXA and ALDO binding to GR and/or MR, FKBP51 is exchanged for FKBP52 facilitating the retrograde movement of the NRs toward the nucleus where they bind to target genes and control their expression. (D) Hsp90 protects PPARγ from degradation. Gelda: geldanamycin, an Hsp90 inhibitor; NE: nuclear envelope.
