Structure of the AML1-ETO NHR3-PKA(RII?) complex and its contribution to AML1-ETO activity.

ABSTRACT: AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RII?)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RII?). Based on this structure, a key residue in AML1-ETO for PKA(RII?) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RII?) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.

SUBMITTER: Corpora T 

PROVIDER: S-EPMC2945414 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature