Molecular and genetic characterization of GABPβ

Fabienne Charles De La Brousse, Edward H. Birkenmeier, David S. King, Lucy B. Rowe, Steven L. McKnight

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

This report outlines three observations relating to GABPβ, a polypeptide constituent of the heterotetrameric transcription factor GABP. Evidence is presented showing that the mouse genome encodes two highly related GABPβ polypeptides, designated GABPβ1-1 and GABPβ2-1. Genomic and cDNA copies of the newly defined Gabpb2 gene were cloned and characterized, providing the conceptually translated amino acid sequence of GABPβ2-1. The genes encoding these two proteins, as well as GABPα, were mapped to three unlinked chromosomal loci. Although physically unlinked, the patterns of expression of the three genes were strikingly concordant. Finally, the molecular basis of GABPβ dimerization was resolved. Carboxy-terminal regions of the two GABPβ polypeptides, which mediate dimerization, bear highly related primary amino acid sequences. Both sequences are free of α-helix destabilizing residues and, when displayed on idealized α-helical projections, reveal marked amphipathy. Two observations indicate that these regions adopt an α-helical conformation and intertwine as coiled-coils. First, the dimer-forming region of GABPβ2-1 can functionally replace the leucine zipper of a bZIP transcription factor. Second, a synthetic peptide corresponding to this region shows distinctive helical properties when examined by circular dichroism spectroscopy. Finally, evidence is presented showing that GABPβ1- 1 and GABPβ2-1 can heterodimerize through this carboxy-terminal domain, but neither protein can heterodimerize via the dimer-forming region of the bZIP protein C/EBPβ.

Original languageEnglish (US)
Pages (from-to)1853-1865
Number of pages13
JournalGenes and Development
Volume8
Issue number15
StatePublished - Jan 1 1994

Keywords

  • GABPβ
  • coiled-coil
  • dimerization
  • gene expression
  • transcription complexes
  • α- helical

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    De La Brousse, F. C., Birkenmeier, E. H., King, D. S., Rowe, L. B., & McKnight, S. L. (1994). Molecular and genetic characterization of GABPβ. Genes and Development, 8(15), 1853-1865.