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Direct regulation of BCL-2 by FLI-1 is involved in the survival of FLI-1-transformed erythroblasts.
- Source :
-
EMBO Journal . 2/15/2002, Vol. 21 Issue 4, p694-703. 10p. - Publication Year :
- 2002
-
Abstract
- Rearrangement of the FLI-1 locus with ensuing overexpression of ELI-1 is an early event in Friend murine leukemia virus-induced disease. When over-expressed in primary erythroblasts, ELI-1 blocks erythropoeitin (Epo)-induced terminal differentiation and inhibits apoptosis normally induced in response to Epo withdrawal. We show here that the survival-inducing property of ELI-i is associated with increased tran- scription of BCL-2. We further show that ELI-1 binds BCL-2 promoter sequences in transformed erythroblasts, and in vitro studies identify specific ELI-1-binding sites essential for the transactivation of the BCL-2 promoter by ELI-1. Analysis of ELI-1 mutants showed a correlation between the ability of ELI-1 to transactivate BCL-2 promoter sequences and their ability to inhibit apoptosis in the absence of Epo. Moreover, inhibitor studies confirmed the essential rote of BCL-2 for ELI-1-transformed erythroblast survival. Finally, enforced expression of BCL-2 was sufficient to pro- mote survival and terminal differentiation of erythroblasts in the absence of Epo. These results show that BCL-2 is an in vivo target of ELI-1 in ELI-1-transformed erythroblasts and that its deregulated expression is instrumental in the survival of these cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 21
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 12955665
- Full Text :
- https://doi.org/10.1093/emboj/21.4.694