Mapping the human glucocorticoid receptor for leukemic cell death

We have mapped the regions of the glucocorticoid receptor important for killing the cells of a line of human leukemic lymphoblasts. The results show that the glucocorticoid response element-specific DNA binding domain is essential, and that only the sequence including the amino acids that subsume the first zinc finger through about half of the second zinc finger are absolutely necessary. Furthermore, in contrast to assays of receptor mutants for ability to increase gene transcription, deletion of the steroid binding domain results in a functionally constitutive receptor fully as active for cell kill as is the holoreceptor after addition of ligand. Deletion of most known transcription-activation, dimerization, ligand-binding, and nuclear translocation regions still leaves a receptor fragment highly potent for cell lethality. The results suggest that delivery systems for such a fragment could result in effective new therapies for certain malignancies.