Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions.

Meyers S, Downing JR, Hiebert SW
Mol Cell Biol. 1993 13 (10): 6336-45

PMID: 8413232 · PMCID: PMC364692 · DOI:10.1128/mcb.13.10.6336

The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) translocation associated with acute myelogenous leukemia and encodes a protein with a central 118-amino-acid domain with 69% homology to the Drosophila pair-rule gene, runt. We demonstrate that AML-1 is a DNA-binding protein which specifically interacts with a sequence belonging to the group of enhancer core motifs, TGT/cGGT. Electrophoretic mobility shift analysis of cell extracts identified two AML-1-containing protein-DNA complexes whose electrophoretic mobilities were slower than those of complexes formed with AML-1 produced in vitro. Mixing of in vitro-produced AML-1 with cell extracts prior to gel mobility shift analysis resulted in the formation of higher-order complexes. Deletion mutagenesis of AML-1 revealed that the runt homology domain mediates both sequence-specific DNA binding and protein-protein interactions. The hybrid product, AML-1/ETO, which results from the (8;21) translocation and retains the runt homology domain, both recognizes the AML-1 consensus sequence and interacts with other cellular proteins.

MeSH Terms (21)

Animals Base Sequence Cell Line Chromosomes, Human, Pair 21 Core Binding Factor Alpha 2 Subunit DNA DNA-Binding Proteins Drosophila Drosophila Proteins Enhancer Elements, Genetic Humans Leukemia, Myeloid, Acute Molecular Sequence Data Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins Transcription, Genetic Transcription Factors Translocation, Genetic Tumor Cells, Cultured

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