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 th...

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Bibliographic Details
Published in:The Journal of biological chemistry 1991-07, Vol.266 (20), p.12976-12980
Main Authors: NAZARETH, L. V, HARBOUR, D. V, THOMPSON, E. B
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Cell Line
Cell Survival
Chickens
Dexamethasone - pharmacology
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
General aspects
Genetic Vectors
Humans
Leukemia
Medical sciences
Pharmacology. Drug treatments
Receptors, Glucocorticoid - drug effects
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - physiology
Receptors, Progesterone - genetics
Receptors, Progesterone - physiology
Transcription, Genetic
Transfection
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)98791-0