Heat shock protein-bound receptors

Fig. 4.4. The principle of signal transduction by nuclear receptors. Nuclear receptors are ligand-controlled transcription factors that bind cognate DNA sequences, or hormone responsive elements (HRE). The hormone acts as a regulating ligand. Most nuclear receptors bind their cognate HREs, which tend to be symmetrically organized, as homo- or heterodimers. The DNA-bound, activated receptor stimulates transcription initiation via direct or indirect protein-protein interactions with the transcription initiation complex. The arrows demonstrate the different possible configurations of the HRE (see also 4.6). H hormone Hsp heat shock protein.

Plasma estrogens in the blood and interstitial fluid are bound to SHBG, from which they dissociate to enter the cell and bind to their receptor. Two genes code for two estrogen receptor isoforms, and 3, which are members of the superfamily of steroid, sterol, retinoic acid, and thyroid receptors. The estrogen receptors are found predominantly in the nucleus bound to heat shock proteins that stabilize them (see Figure 39-4). 

Based on physiochemical properties, single-step immunoaffinity purified B-receptors were in the native transformed state. Isolated receptors were maintained as undegraded 120 kDa doublets (Fig. 2) they retained their hormone binding activity and they displayed the correct steroid specificity for PR. Isolated B-receptors also bound efficiently to DNA-cellulose requiring 0.25 M salt for their release. They sedimented as 4S monomers on salt-containing sucrose gradients and as a 6S peak in the absence of salt. All these confirm their transformed state. In addition, under these conditions, purified B-receptors were free of the 90 kDa receptor-associated heat shock protein that always copurifies with 8S untransformed receptors in other... 

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