Domains of Transcription Activation Transactivators

Alternative mRNA maturation is frequent in tumor tissue expressing ER. In some cases it would give rise to truncated receptors that would maintain the capacity to bind hormones but would have lost their capacity as a transcription factor. Additionally, truncated receptors would be produced that would lack the capacity to bind hormones but would conserve intact their capacity to interact with DNA. In this case, the truncated receptors can become tumorigenic by stimulating the proliferation of cells uncontrolled by hormones. These receptor variants have been the object of exhaustive study at the level of mRNA in tumors of the breast, mainly estrogen-dependent tumors (Clemons et al. 2001 Garcia et al. 1988 Palmieri et al. 2002), but tests for the existence of receptor protein with these characteristics have not corroborated the expectation created by their theoretical interest. 

In cell cultures deprived of hormones or in target organs of ovariectomized animals, ERs are found in a state known as native , characterized by their association with several proteins (Redeuilh et al. 1987). The best known are hsp90 and p59. 

From what has been discovered, it can be deduced that part of the functions of ERs remains hidden in the native state. Interaction with hormone causes this structure to come apart. This process of activation or transformation permits the receptor to exhibit all the potential of interaction with DNA and makes the receptor exhibit the properties that were hidden by the proteins that accompanied it in the 8S form (McGuire et al. 1991). 

All nuclear receptors have sequences known as domains of nuclear location (Picard et al. 1987). These sequences, rich in arginine and lysine, confer upon the many proteins that contain them the capacity to bind to nonhistone nuclear proteins. Receptors have up to four of these sequences, whose cooperation is necessary for nuclear location. When these sequences are exposed, the receptor 

In the case of the ER, when a region of 20 amino acids between 250 and 270 is missing, the receptor is located strictly in the cytoplasm. Domains of similar size and function have also been located in the receptors of glucocorticoids and of progesterone. The zone of nuclear location overlaps with one of the sequences for interacting with hsp90, which at the same time is next to the DBD. The coincidence of the three functions in a space so restricted implies that they are totally or partly incompatible sterically (Evans 1989 Gruber et al. 2002). 

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