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PMID: 9343407 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins.

Molecular and cellular biology ·Vol. 17 ·No. 11 ·1997-11-00 ·Pages 6448-58

Shen WF, Montgomery JC, Rozenfeld S, Moskow JJ, Lawrence HJ, Buchberg AM, Largman C

Abstract

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

MeSH Terms
Animals Cell Transformation, Neoplastic/genetics DNA/metabolism DNA-Binding Proteins/metabolism Drosophila Proteins Homeodomain Proteins/classification,metabolism Leukemia, Myeloid/genetics Mice Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins/metabolism Protein Binding
Chemicals
Abd-B proteins, Drosophila DNA-Binding Proteins Drosophila Proteins Homeodomain Proteins Meis1 protein, mouse Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins homeobox protein HOXA9 DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shen W F
Department of Medicine, University of California VA Medical Center, San Francisco 94121, USA.
Montgomery J C
Rozenfeld S
Moskow J J
Lawrence H J
Buchberg A M
Largman C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.11.6448
Published
1997-11-00
Pages
6448-58
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC232497
Subset
IM
Grants
NIDDK NIH HHS · N44DK-3-2219 · United States
NCI NIH HHS · P01CA 21124 · United States
NIDDK NIH HHS · R01 DK48642 · United States
External Links
PubMed source DOI: 10.1128/MCB.17.11.6448 PMC Full Text View journal details
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