E protein silencing by the leukemogenic AML1-ETO fusion protein.

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.
Mesh Terms:
Acute Disease, Amino Acid Sequence, Basic Helix-Loop-Helix Transcription Factors, CREB-Binding Protein, Cell Line, Cell Line, Tumor, Conserved Sequence, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Gene Silencing, Hela Cells, Hematopoietic Stem Cells, Humans, Jurkat Cells, Leukemia, Myeloid, Molecular Sequence Data, Nuclear Proteins, Oncogene Proteins, Fusion, Protein Binding, Protein Structure, Tertiary, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transcriptional Activation, Translocation, Genetic
Date: Aug. 27, 2004
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