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Mapping the human glucocorticoid receptor for leukemic cell death

Authors :
E B Thompson
D. V. Harbour
L.V. Nazareth
Source :
Journal of Biological Chemistry. 266:12976-12980
Publication Year :
1991
Publisher :
Elsevier BV, 1991.

Abstract

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.

Details

ISSN :
00219258
Volume :
266
Database :
OpenAIRE
Journal :
Journal of Biological Chemistry
Accession number :
edsair.doi...........18a775adf5c6ab641b7f69666e1eb4ec
Full Text :
https://doi.org/10.1016/s0021-9258(18)98791-0