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

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(RIIα)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIα). Based on this structure, a key residue in AML1-ETO for PKA(RIIα) 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(RIIα) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.

Corpora T ，Roudaia L ，Oo ZM ，Chen W ，Manuylova E ，Cai X ，Chen MJ ，Cierpicki T ，Speck NA ，Bushweller JH ... -  《-》

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

Park S ，Chen W ，Cierpicki T ，Tonelli M ，Cai X ，Speck NA ，Bushweller JH ... -  《-》

The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity.

Liu Y ，Cheney MD ，Gaudet JJ ，Chruszcz M ，Lukasik SM ，Sugiyama D ，Lary J ，Cole J ，Dauter Z ，Minor W ，Speck NA ，Bushweller JH ... -  《CANCER CELL》

The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia.

Vangala RK ，Heiss-Neumann MS ，Rangatia JS ，Singh SM ，Schoch C ，Tenen DG ，Hiddemann W ，Behre G ... -  《BLOOD》

Disruption of the NHR4 domain structure in AML1-ETO abrogates SON binding and promotes leukemogenesis.

Ahn EY ，Yan M ，Malakhova OA ，Lo MC ，Boyapati A ，Ommen HB ，Hines R ，Hokland P ，Zhang DE ... -  《-》