Molecular basis of the mixed lineage leukemia-menin interaction: implications for targeting mixed lineage leukemias.

ABSTRACT: Chromosomal translocations targeting the mixed lineage leukemia (MLL) gene result in MLL fusion proteins that are found in aggressive human acute leukemias. Disruption of MLL by such translocations leads to overexpression of Hox genes, resulting in a blockage of hematopoietic differentiation that ultimately leads to leukemia. Menin, which directly binds MLL, has been identified as an essential oncogenic co-factor required for the leukemogenic activity of MLL fusion proteins. Here, we characterize the molecular basis of the MLL-menin interaction. Using (13)C-detected NMR experiments, we have mapped the residues within the intrinsically unstructured fragment of MLL that are required for binding to menin. Interestingly, we found that MLL interacts with menin with a nanomolar affinity (K(d) ∼

SUBMITTER: Grembecka J 

PROVIDER: S-EPMC3003368 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature