Author/Authors :
Liu، نويسنده , , Yizhou and Cheney، نويسنده , , Matthew D. and Gaudet، نويسنده , , Justin J. and Chruszcz، نويسنده , , Maksymilian and Lukasik، نويسنده , , Stephen M. and Sugiyama، نويسنده , , Daisuke and Lary، نويسنده , , Jeff and Cole، نويسنده , , James and Dauter، نويسنده , , Zbyszek and Minor، نويسنده , , Wladek and Speck، نويسنده , , Nancy A. and Bushweller، نويسنده , , John H.، نويسنده ,
Abstract :
Summary
TO is the chimeric protein resulting from the t(8;21) in acute myeloid leukemia. The Nervy homology 2 (NHR2) domain in ETO mediates oligomerization and AML1/ETOʹs interactions with ETO, MTGR1, and MTG16, and with the corepressor molecules mSin3A and HDAC1 and HDAC3. We solved the NHR2 domain structure and found it to be an α-helical tetramer. We show that oligomerization contributes to AML1/ETOʹs inhibition of granulocyte differentiation, is essential for its ability to enhance the clonogenic potential of primary mouse bone marrow cells, and affects AML1/ETOʹs activity on several endogenous genes. Oligomerization is also required for AML1/ETOʹs interactions with ETO, MTGR1, and MTG16, but not with other corepressor molecules.
