Direct regulation of BCL-2 by FLI-1 is involved in the survival of FLI-1-transformed erythroblasts

作者：Lesault I; Quang CT; Frampton J; Ghysdael J^*

来源：The EMBO Journal, 2002, 21(4): 694-703.

DOI：10.1093/emboj/21.4.694

• BCL-2
• erythroblast survival
• FLI-1
• Friend erythroleukemia

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.

• 出版日期2002-2-15