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PMID: 8413232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

Molecular and cellular biology ·Vol. 13 ·No. 10 ·1993-10-00 ·Pages 6336-45

Meyers S, Downing JR, Hiebert SW

Abstract

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.

Related Genes
AML1 ETO
MeSH Terms
Animals Base Sequence Cell Line Chromosomes, Human, Pair 21 Core Binding Factor Alpha 2 Subunit DNA/metabolism DNA-Binding Proteins/genetics,metabolism Drosophila Drosophila Proteins Enhancer Elements, Genetic Humans Leukemia, Myeloid, Acute/genetics Molecular Sequence Data Neoplasm Proteins/genetics,metabolism Nuclear Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins/genetics,metabolism Transcription Factors Transcription, Genetic Translocation, Genetic Tumor Cells, Cultured
Chemicals
Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins Drosophila Proteins Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins RUNX1 protein, human Recombinant Fusion Proteins Transcription Factors run protein, Drosophila DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Meyers S
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Downing J R
Hiebert S W
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47 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.10.6336-6345.1993
Published
1993-10-00
Pages
6336-45
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364692
Subset
IM
Grants
NCI NIH HHS · 5 P30 CA 21765 · United States
NCI NIH HHS · CA 01429 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.10.6336-6345.1993 PMC Full Text View journal details
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