The pathway of leukemic cell death caused by glucocorticoid receptor fragment 465

Mohamed El-Naghy, Betty H. Johnson, Hong Chen, Naseem H. Ansari, Weiping Zhang, Peter Moller, Yan shan Ji, E. Brad Thompson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The truncated glucocorticoid receptor mutant gene 465* codes for a protein that is interrupted by a frameshift mutation in the second zinc finger of the natural DNA binding domain. Thus, 465* represents the natural amino acid sequence 1-465 followed by 21 novel amino acids starting at position 466. The entire ligand binding domain is missing. Prior studies have shown that transient transfection of the glucocorticoid-resistant leukemic T-cell clone ICR-27 with a plasmid expressing 465* rapidly reduces the number of viable cells. This response does not require activation by a steroid, and a hybrid protein consisting of green fluorescent protein fused to 465* is found primarily in the cytoplasm. In the present study, we present evidence that the decrease in cell number is due to a form of cell death that bears many of the classic characteristics of apoptosis. Expression of the 465* protein can be detected a few hours after electroporation and is followed by activation of caspase-3 as well as reduction of the mitochondrial inner transmembrane potential. The caspase-3 inhibitor ZVAD.fmk blocks 465*-dependent cell death when added acutely after electroporation, but fails to do so later. We conclude that the novel 465* gene causes cell death by apoptosis.

Original languageEnglish (US)
Pages (from-to)166-175
Number of pages10
JournalExperimental Cell Research
Issue number2
StatePublished - Nov 1 2001
Externally publishedYes


  • Apoptosis
  • Caspase-3
  • Glucocorticoid receptor fragment
  • Mitochondria
  • T-cell leukemia

ASJC Scopus subject areas

  • Cell Biology


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