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

By Sangho Park, Wei Chen, Tomasz Cierpicki, Marco Tonelli, Xiongwei Cai, Nancy A. Speck and John H. Bushweller

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

Topics: Myeloid Neoplasia
Publisher: American Society of Hematology
OAI identifier: oai:pubmedcentral.nih.gov:2668852
Provided by: PubMed Central
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