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J. Virol., May 1995, 2898-2906, Vol 69, No. 5
AL Zaiman, AF Lewis, BE Crute, NA Speck and J Lenz
Core binding factor (CBF), also known as polyomavirus enhancer-binding
protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor
that binds to an element termed the core within the enhancers of the murine
leukemia virus family of retroviruses. The core elements of the SL3 virus
are important genetic determinants of the ability of this virus to induce
T-cell lymphomas and the transcriptional activity of the viral long
terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA
binding subunit, CBF alpha, and a second subunit, CBF beta, that stimulates
the DNA binding activity of CBF alpha. One of the genes that encodes a CBF
alpha subunit is AML1, also called Cbf alpha 2. This locus is rearranged by
chromosomal translocations in human myeloproliferative disorders and
leukemias. An exogenously expressed Cbf alpha 2-encoded subunit (CBF alpha
2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa
cells. Activity was mediated through the core elements. Three different
isoforms of CBF beta were also tested for transcriptional activity on the
SL3 enhancer. The longest form, CBF beta-187, increased the transcriptional
stimulation by CBF alpha 2-451 twofold in HeLa cells, although it had no
effect in P19 cells. Transcriptional activation by CBF beta required
binding to the CBF alpha subunit, as a form of CBF beta that lacked binding
ability, CBF beta-148, failed to increase activity. These results indicated
that at least in certain cell types, the maximum activity of CBF required
both subunits. They also provided support for the hypothesis that CBF is a
factor in T lymphocytes that is responsible for recognition of the SL3
cores. We also examined whether CBF could distinguish a 1-bp difference
between the enhancer core of SL3 and the core of the nonleukemogenic virus,
Akv. This difference strongly affects transcription in T cells and
leukemogenicity of SL3. However, no combination of CBF alpha and CBF beta
subunits that we tested was able to distinguish the 1-bp difference in
transcription assays. Thus, a complete understanding of how T cells
recognize the SL3 core remains to be elucidated.
Copyright © 1995, American Society for Microbiology
Transcriptional activity of core binding factor-alpha (AML1) and beta subunits on murine leukemia virus enhancer cores
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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