J. Frampton et al., V-MYB OF E26 LEUKEMIA-VIRUS UP-REGULATES BCL-2 AND SUPPRESSES APOPTOSIS IN MYELOID CELLS, Genes & development, 10(21), 1996, pp. 2720-2731
Many oncogenes have been shown to be deregulated transcription factors
, yet direct target genes mediating cell transformation remain elusive
. Here we describe such a target for v-Myb by exploiting a temperature
-sensitive mutant of the E26 avian leukemia virus encoding Myb-Ets. My
eloblasts transformed by the mutant differentiate into macrophages or
die by apoptosis when shifted to the nonpermissive temperature as a re
sult of inactivation of v-Myb. During this process mRNA of the antiapo
ptotic oncoprotein Bcl-2 is down-regulated with kinetics similar to th
ose of Mim-1, a differentiation-related protein whose expression is di
rectly regulated by Myb. Forced expression of bcl-2 rescues the cells
from apoptosis, without preventing either their withdrawal from the ce
ll cycle or their differentiation. v-Myb appears to act directly on th
e bcl-2 gene, because a bcl-2 promoter-driven reporter is activated by
Myb-Ets and v-Myb-VP16 and requires intact Myb binding sites within t
he promoter. Surprisingly, inactivation of v-Myb in multipotent progen
itors transformed by E26 virus does not induce apoptosis, indicating t
hat bcl-2 regulation by the oncoprotein is required for the transforma
tion of some cell types but not others.