Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity
Abstract
AML1/ETO 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/ETO's 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/ETO's effects on proliferation, differentiation, and gene expression.
Department
Molecular, Cellular and Biomedical Sciences
Publication Date
6-12-2007
Journal Title
Cancer Cell
Publisher
Cell Press
Digital Object Identifier (DOI)
Document Type
Article
Recommended Citation
Liu, Y., Chen, W., Gaudet, J., Cheney, M.D., Roudaia, L., Cierpicki, T., Klet, R.C., Hartman, K., Laue, T.M., Speck, N.A., Bushweller, J.H. (2007) “Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity.” Cancer Cell, 11, 483-497.