Author/Authors :
Liu، نويسنده , , Yizhou and Chen، نويسنده , , Wei and Gaudet، نويسنده , , KENNETH S. VECCHIO and
JUSTIN L. CHENEY، نويسنده , , Matthew D. and Roudaia، نويسنده , , Liya and Cierpicki، نويسنده , , Tomasz and Klet، نويسنده , , Rachel C. and Hartman، نويسنده , , Kari and Laue، نويسنده , , Thomas M. and Speck، نويسنده , , Nancy A. and Bushweller، نويسنده , , John H.، نويسنده ,
Abstract :
Summary
TO results from the t(8;21) associated with 12%–15% of acute myeloid leukemia. The AML1/ETO MYND domain mediates interactions with the corepressors SMRT and N-CoR and contributes to AML1/ETOʹs ability to repress proliferation and differentiation of primary bone marrow cells as well as to enhance their self renewal in vitro. We solved the solution structure of the MYND domain and show it to be structurally homologous to the PHD and RING finger families of proteins. We also determined the solution structure of an MYND-SMRT peptide complex. We demonstrated that a single amino acid substitution that disrupts the interaction between the MYND domain and the SMRT peptide attenuated AML1/ETOʹs effects on proliferation, differentiation, and gene expression.
