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Blood. 2009 Apr 9;113(15):3558-67. doi: 10.1182/blood-2008-06-161307. Epub 2009 Feb 9.

Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity.

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  • 1Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.

Abstract

AML1-ETO is the chimeric protein product of the t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the eTAFH domain, which is homologous to several TATA binding protein-associated factors (TAFs) and interacts with E proteins (E2A and HEB). It has been proposed that AML1-ETO-mediated silencing of E protein function might be important for t(8;21) leukemogenesis. Here, we determined the solution structure of a complex between the AML1-ETO eTAFH domain and an interacting peptide from HEB. On the basis of the structure, key residues in AML1-ETO for HEB association were mutated. These mutations do not impair the ability of AML1-ETO to enhance the clonogenic capacity of primary mouse bone marrow cells and do not eliminate its ability to repress proliferation or granulocyte differentiation. Therefore, the eTAFH-E protein interaction appears to contribute relatively little to the activity of AML1-ETO.

PMID:
19204326
[PubMed - indexed for MEDLINE]
PMCID:
PMC2668852
Free PMC Article

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