Direct regulation of the bcl-2 gene by Fli-1 is involved in the survival of Fli-1-transformed erythroblasts

I Lesault, C Tran-Quang, Jonathan Frampton, J Ghysdael

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Rearrangement of the FLI-1 locus with ensuing overexpression of FLI-1 is an early event in Friend murine leukemia virus-induced disease. When overexpressed in primary erythroblasts, FLI-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 FLI-1 is associated with increased transcription of BCL-2. We further show that FLI-1 binds BCL-2 promoter sequences in transformed erythroblasts, and in vitro studies identify specific FLI-1-binding sites essential for the transactivation of the BCL-2 promoter by FLI-1. Analysis of FLI-1 mutants showed a correlation between the ability of FLI-1 to transactivate BCL-2 promoter sequences and their ability to inhibit apoptosis in the absence of Epo. Moreover, inhibitor studies confirmed the essential role of BCL-2 for FLI-1-transformed erythroblast survival. Finally, enforced expression of BCL-2 was sufficient to promote survival and terminal differentiation of erythroblasts in the absence of Epo. These results show that BCL-2 is an in vivo target of FLI-1 in FLI-1-transformed erythroblasts and that its deregulated expression is instrumental in the survival of these cells.
Original languageEnglish
Pages (from-to)694-703
Number of pages10
JournalThe EMBO journal
Volume21
Issue number4
DOIs
Publication statusPublished - 15 Feb 2002

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