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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Apoptosis, Calcium-Binding Proteins, Carrier Proteins, Caspase 3, Caspases, DNA, Electrophoretic Mobility Shift Assay, Fusion Proteins, bcr-abl, Humans, Jurkat Cells, K562 Cells, Kv Channel-Interacting Proteins, Leukemia, Protein Binding, Protein-Tyrosine Kinases, Repressor Proteins, Signal Transduction, fas Receptor.
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Do fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells? Context: The apoptotic Bcl-2 family member Hrk is transcriptionally silenced via DREAM in hematopoietic progenitor cell lines, and is specifically induced after growth factor withdrawal. Given that expression of Hrk is sufficient to induce apoptosis, we studied the expression of this apoptotic protein and its regulatory mechanism in human leukemia cells. K562 chronic myeloid leukemia cells were treated with STI571, a Bcr-Abl kinase inhibitor, and the Jurkat T-cell leukemia cell line was incubated with agonistic anti-Fas antibodies. Following treatment, we correlated the expression of Hrk protein with the DNA binding capacity of DREAM, and the induction of apoptosis. We show that treatment of K562 with STI571 blocks the binding of DREAM to the Hrk gene and allows the expression of Hrk, which correlates with the induction of apoptosis. Similarly, treatment of Jurkat cells with agonistic anti-Fas antibodies triggers the expression of Hrk through DREAM inactivation. Interestingly, inhibition of caspases, by culturing Jurkat cells in the presence of z-VAD-fmk, abrogates Fas-mediated hrk expression and apoptosis. Furthermore, in vitro analysis shows that active recombinant caspase-3 releases a fragment from the DREAM protein, suggesting that caspase-3 may be upstream of DREAM.
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These data suggest that apoptosis inducers as diverse as oncoprotein inhibitors and cell death receptor activators trigger Hrk expression via blockade of DREAM in leukemia cells, and this apoptotic pathway may be regulated, at least in some systems, by the proteolytic activity of caspase-3. Final Decision: yes