1. E protein silencing by the leukemogenic AML1-ETO fusion protein
- Author
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Zhang, Jinsong, Kalkum, Markus, Yamamura, Soichiro, Chait, Brian T., and Roeder, Robert G.
- Subjects
Leukemia -- Genetic aspects -- Research -- Physiological aspects ,Chromosome abnormalities -- Research -- Genetic aspects -- Physiological aspects ,Science and technology ,Physiological aspects ,Research ,Genetic aspects - Abstract
The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 15% of acute myeloid leukemia (AML) cases. This study shows that AML1-ETO, as well as ETO, inhibits transcriptional activation by E proteins through stable interactions that preclude recruitment of p300/CREB-binding protein (CBP) coactivators. These interactions are mediated by a conserved ETO TAF4 homology domain and a 17-amino acid p300/CBP and ETO target motif within AD1 activation domains of E proteins. In t(8;21) leukemic cells, very stable interactions between AML1-ETO and E proteins underlie a t(8;21) translocation-specific silencing of E protein function through an aberrant cofactor exchange mechanism. These studies identify E proteins as AML1-ETO targets whose dysregulation may be important for t(8;21) leukemogenesis, as well as an E protein silencing mechanism that is distinct from that associated with differentiation-inhibitory proteins., The t(8;21) chromosomal translocation fuses an N-terminal region of the AML1 transcription factor to a nearly complete ETO protein and is one of the most frequent chromosomal abnormalities seen in [...]
- Published
- 2004