| Literature DB >> 20708017 |
Takeshi Corpora1, Liya Roudaia, Zaw Min Oo, Wei Chen, Ekaterina Manuylova, Xiongwei Cai, Michael J Chen, Tomasz Cierpicki, Nancy A Speck, John H Bushweller.
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(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.Entities:
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Year: 2010 PMID： 20708017 PMCID： PMC2945414 DOI： 10.1016/j.jmb.2010.08.007
Source DB: PubMed Journal: J Mol Biol ISSN： 0022-2836 Impact factor: 5.469