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NRS 12, e005 | Figure 1

Cato L, Neeb A, Brown M and Cato AC (2014) Control of steroid receptor dynamics and function by genomic actions of the cochaperones p23 and Bag-1L. Nucl Recept Signal 12, e005. doi:10.1621/nrs.12005


Figure 1: A model depicting some of the key steps of the maturation pathway of steroid receptors. (A) Binding of the Hsp90, p23 and a preassembled complex of Hop, Hsp70 and Hsp40 assists a mature folding of the steroid receptor (SR). Cytoplasmic Bag-1 isoforms (Bag-1, -1M, -1S) control this process and mediate proteasomal degradation of misfolded SRs. Addition of Hsp90-dimers and p23 complete the assembled complex, termed the “foldosome” (B). Release of Hop, Hsp70 and Hsp40 and addition of any one of the TPR-containing cochaperones, for example FKBP51 (as shown here), further stabilize the SR in a high affinity form (C). After ligand binding FKBP51 is replaced by FKBP52, which mediates translocation to the nucleus via the microtubuli system (via dynein and dynamitin) in a molecular complex termed the “transportosome” (D). Within the nucleus FKBP52 is released and the receptor binds the response elements as an active dimer. Cochaperones, such as p23 and Bag-1L (that has been described to bind to chromatin prior to the nuclear entry of the receptor), enhance the activity of the SR most likely by stabilizing the active state of the receptor. The molecular chaperones Hsp90 and Hsp70 possibly also play a role in this process (E).