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PMID: 8698039 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Engrailed and Hox homeodomain proteins contain a related Pbx interaction motif that recognizes a common structure present in Pbx.

The EMBO journal ·Vol. 15 ·No. 13 ·1996-07-01 ·Pages 3385-93

Peltenburg LT, Murre C

Abstract

Hox gene products have the ability to interact with either extradenticle or pbx gene products to bind cooperatively to DNA. The region in Hox proteins that is required for this interaction is located N-terminal of the homeodomain and contains a highly conserved hexapeptide. We now show that the engrailed gene products also contain a Pbx interaction motif positioned within a previously conserved region, the EH2 domain. The EH2 domain is located N-terminal of the homeodomain. Two tryptophan residues present in the Drosophila and murine Engrailed EH2 domain are required for cooperativity with extradenticle and Pbx, respectively. A second conserved domain, EH3, is required as well for cooperativity with Pbx, since deletions or an insertion in this region reduce cooperative DNA binding. Peptides containing the Pbx interaction motif of either Engrailed or Hox are capable of destabilizing Engrailed-Pbx and Hox-Pbx cooperative DNA binding. These data indicate that the Pbx interaction motifs present in Hox and engrailed gene products recognize a common structure present in the Pbx family of homeodomain proteins.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Biological Evolution DNA Probes DNA-Binding Proteins/genetics,metabolism Drosophila Proteins Homeodomain Proteins/genetics,metabolism Humans Insect Hormones/genetics,metabolism Molecular Sequence Data Pre-B-Cell Leukemia Transcription Factor 1 Protein Binding Proto-Oncogene Proteins/metabolism Transcription Factors/genetics,metabolism
Chemicals
DNA Probes DNA-Binding Proteins Drosophila Proteins En protein, Drosophila Homeodomain Proteins Insect Hormones Pre-B-Cell Leukemia Transcription Factor 1 Proto-Oncogene Proteins Transcription Factors exd protein, Drosophila pbx1 protein, human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Peltenburg L T
Department of Biology 0366, University of California, San Diego, La Jolla, CA 92093, USA.
Murre C
References (38)
38 references, click to expand
  1. Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions.
    Dev Genet. 1992;13(5):345-58 PMID: 1363401
  2. A short, disordered protein region mediates interactions between the homeodomain of the yeast alpha 2 protein and the MCM1 protein.
    Cell. 1993 Jan 15;72(1):105-12 PMID: 8422672
  3. Dpbx, a new homeobox gene closely related to the human proto-oncogene pbx1 molecular structure and developmental expression.
    Mech Dev. 1993 May;41(2-3):155-61 PMID: 8100142
  4. extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1.
    Cell. 1993 Sep 24;74(6):1101-12 PMID: 8104703
  5. Ectopic expression and function of the Antp and Scr homeotic genes: the N terminus of the homeodomain is critical to functional specificity.
    Development. 1993 Jun;118(2):339-52 PMID: 7900989
  6. Determination of the nuclear magnetic resonance solution structure of an Antennapedia homeodomain-DNA complex.
    J Mol Biol. 1993 Dec 20;234(4):1084-93 PMID: 7903398
  7. Homeobox genes: their function in Drosophila segmentation and pattern formation.
    Cell. 1994 Jul 29;78(2):181-9 PMID: 7913879
  8. Hox genes in vertebrate development.
    Cell. 1994 Jul 29;78(2):191-201 PMID: 7913880
  9. Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins.
    EMBO J. 1994 Aug 1;13(15):3561-9 PMID: 7914871
  10. The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein.
    Cell. 1994 Aug 26;78(4):603-15 PMID: 7915199
  11. extradenticle raises the DNA binding specificity of homeotic selector gene products.
    Cell. 1994 Aug 26;78(4):617-24 PMID: 7915200
  12. Interaction between two homeodomain proteins is specified by a short C-terminal tail.
    Nature. 1994 Sep 29;371(6496):429-32 PMID: 8090224
  13. Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction.
    Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):739-43 PMID: 7846045
  14. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins.
    Genes Dev. 1995 Mar 15;9(6):663-74 PMID: 7729685
  15. Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the products of multiple murine Hox genes, some of which are themselves oncogenes.
    Mol Cell Biol. 1995 Jul;15(7):3786-95 PMID: 7791786
  16. Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx.
    Cell. 1995 Jun 30;81(7):1031-42 PMID: 7600572
  17. Cooperative interactions between HOX and PBX proteins mediated by a conserved peptide motif.
    Mol Cell Biol. 1995 Aug;15(8):3989-97 PMID: 7623795
  18. The pentapeptide motif of Hox proteins is required for cooperative DNA binding with Pbx1, physically contacts Pbx1, and enhances DNA binding by Pbx1.
    Mol Cell Biol. 1995 Oct;15(10):5811-9 PMID: 7565734
  19. The hexapeptide LFPWMR in Hoxb-8 is required for cooperative DNA binding with Pbx1 and Pbx2 proteins.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9166-70 PMID: 7568094
  20. Crystal structure of the MATa1/MAT alpha 2 homeodomain heterodimer bound to DNA.
    Science. 1995 Oct 13;270(5234):262-9 PMID: 7569974
  21. The pancreatic islet factor STF-1 binds cooperatively with Pbx to a regulatory element in the somatostatin promoter: importance of the FPWMK motif and of the homeodomain.
    Mol Cell Biol. 1995 Dec;15(12):7091-7 PMID: 8524276
  22. Hox gene products modulate the DNA binding activity of Pbx1 and Pbx2.
    Mech Dev. 1995 Jul;52(1):99-108 PMID: 7577680
  23. Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins.
    Nature. 1984 Jul 5-11;310(5972):25-31 PMID: 6330566
  24. Divergent homeo box proteins recognize similar DNA sequences in Drosophila.
    Nature. 1988 Apr 28;332(6167):858-61 PMID: 2895896
  25. The sequence specificity of homeodomain-DNA interaction.
    Cell. 1988 Sep 23;54(7):1081-90 PMID: 3046753
  26. The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes.
    EMBO J. 1989 May;8(5):1497-505 PMID: 2569969
  27. A homeodomain substitution changes the regulatory specificity of the deformed protein in Drosophila embryos.
    Cell. 1989 Nov 3;59(3):563-71 PMID: 2572328
  28. Calculation of protein extinction coefficients from amino acid sequence data.
    Anal Biochem. 1989 Nov 1;182(2):319-26 PMID: 2610349
  29. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.
    Cell. 1990 Feb 23;60(4):535-45 PMID: 1967982
  30. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL.
    Cell. 1990 Feb 23;60(4):547-55 PMID: 1967983
  31. The specificities of Sex combs reduced and Antennapedia are defined by a distinct portion of each protein that includes the homeodomain.
    Cell. 1990 Sep 21;62(6):1087-103 PMID: 1976044
  32. Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity.
    Genes Dev. 1990 Jul;4(7):1209-23 PMID: 1976570
  33. Coordinate regulation of HOX genes in human hematopoietic cells.
    Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6348-52 PMID: 1712489
  34. PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1.
    Mol Cell Biol. 1991 Dec;11(12):6149-57 PMID: 1682799
  35. Homeobox genes and axial patterning.
    Cell. 1992 Jan 24;68(2):283-302 PMID: 1346368
  36. Mapping functional specificity in the Dfd and Ubx homeo domains.
    Genes Dev. 1992 Jun;6(6):1071-81 PMID: 1350559
  37. NMR structure determination reveals that the homeodomain is connected through a flexible linker to the main body in the Drosophila Antennapedia protein.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10738-42 PMID: 1359544
  38. The segment identity functions of Ultrabithorax are contained within its homeo domain and carboxy-terminal sequences.
    Genes Dev. 1993 May;7(5):796-811 PMID: 8098307
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-07-01
Pages
3385-93
Language
English
Region
England
NLM ID
8208664
PMCID
PMC451902
Subset
IM
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