Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins

Ching-Pin Chang, W. F. Shen, S. Rozenfeld, H. J. Lawrence, C. Largman, M. L. Cleary

Research output: Contribution to journalArticle

339 Citations (Scopus)

Abstract

The human proto-oncogene PBX1 codes for a homolog of Drosophila extradenticle, a divergent homeo domain protein that modulates the developmental and DNA-binding specificity of select HOM proteins. We demonstrate that wild-type Pbx proteins and chimeric E2a-Pbx1 oncoproteins cooperatively bind a consensus DNA probe with HoxB4, B6, and B7 of the Antennapedia class of Hox/HOM proteins. Specificity of Hox-Pbx interactions was suggested by the inability of Pbx proteins to cooperatively bind the synthetic DNA target with HoxA10 or Drosophila even-skipped. Site-directed mutagenesis showed that the hexapeptide motif (IYPWMK) upstream of the Hox homeo domain was essential for HoxB6 and B7 to cooperatively bind DNA with Pbx proteins. Engraftment of the HoxB7 hexapeptide onto HoxA10 endowed it with robust cooperative properties, demonstrating a functional role for the highly conserved hexapeptide element as one of the molecular determinants delimiting Hox-Pbx cooperativity. The Pbx homeo domain was necessary but not sufficient for cooperativity, which required conserved amino acids carboxy- terminal of the homeo domain. These findings demonstrate that interactions between Hox and Pbx proteins modulate their DNA-binding properties, suggesting that Pbx and Hox proteins act in parallel as heterotypic complexes to regulate expression of specific subordinate genes.

Original languageEnglish (US)
Pages (from-to)663-674
Number of pages12
JournalGenes and Development
Volume9
Issue number6
StatePublished - 1995
Externally publishedYes

Fingerprint

DNA
Proteins
Drosophila
Homeodomain Proteins
Proto-Oncogenes
Oncogene Proteins
DNA Probes
Site-Directed Mutagenesis
Amino Acids
Genes

Keywords

  • E2a-Pbx1
  • homeo domain proteins
  • Hox
  • Pbx
  • proto-oncogene

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Chang, C-P., Shen, W. F., Rozenfeld, S., Lawrence, H. J., Largman, C., & Cleary, M. L. (1995). Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes and Development, 9(6), 663-674.

Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. / Chang, Ching-Pin; Shen, W. F.; Rozenfeld, S.; Lawrence, H. J.; Largman, C.; Cleary, M. L.

In: Genes and Development, Vol. 9, No. 6, 1995, p. 663-674.

Research output: Contribution to journalArticle

Chang, C-P, Shen, WF, Rozenfeld, S, Lawrence, HJ, Largman, C & Cleary, ML 1995, 'Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins', Genes and Development, vol. 9, no. 6, pp. 663-674.
Chang C-P, Shen WF, Rozenfeld S, Lawrence HJ, Largman C, Cleary ML. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes and Development. 1995;9(6):663-674.
Chang, Ching-Pin ; Shen, W. F. ; Rozenfeld, S. ; Lawrence, H. J. ; Largman, C. ; Cleary, M. L. / Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. In: Genes and Development. 1995 ; Vol. 9, No. 6. pp. 663-674.
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