Molecular and genetic characterization of GABP

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

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 GABPβ 1-1 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-tenninal 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 - 1994

Fingerprint

Molecular Biology
Basic-Leucine Zipper Transcription Factors
Peptides
Dimerization
Amino Acid Sequence
GA-Binding Protein Transcription Factor
Leucine Zippers
Circular Dichroism
Protein C
Genes
Spectrum Analysis
Complementary DNA
Genome
Gene Expression
Proteins

Keywords

  • α-helical
  • Coiled-coil
  • Dimerization
  • Gabpβ
  • Gene expression
  • Transcription complexes

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

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

Molecular and genetic characterization of GABP. / De La Brousse, Fabienne Charles; Birkenmeier, Edward H.; King, David S.; Rowe, Lucy B.; McKnight, Steven L.

In: Genes and Development, Vol. 8, No. 15, 1994, p. 1853-1865.

Research output: Contribution to journalArticle

De La Brousse, FC, Birkenmeier, EH, King, DS, Rowe, LB & McKnight, SL 1994, 'Molecular and genetic characterization of GABP', Genes and Development, vol. 8, no. 15, pp. 1853-1865.
De La Brousse FC, Birkenmeier EH, King DS, Rowe LB, McKnight SL. Molecular and genetic characterization of GABP. Genes and Development. 1994;8(15):1853-1865.
De La Brousse, Fabienne Charles ; Birkenmeier, Edward H. ; King, David S. ; Rowe, Lucy B. ; McKnight, Steven L. / Molecular and genetic characterization of GABP. In: Genes and Development. 1994 ; Vol. 8, No. 15. pp. 1853-1865.
@article{11af291af84d41d9b3eabfeb31955c59,
title = "Molecular and genetic characterization of GABP",
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 GABPβ 1-1 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-tenninal 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.",
keywords = "α-helical, Coiled-coil, Dimerization, Gabpβ, Gene expression, Transcription complexes",
author = "{De La Brousse}, {Fabienne Charles} and Birkenmeier, {Edward H.} and King, {David S.} and Rowe, {Lucy B.} and McKnight, {Steven L.}",
year = "1994",
language = "English (US)",
volume = "8",
pages = "1853--1865",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "15",

}

TY - JOUR

T1 - Molecular and genetic characterization of GABP

AU - De La Brousse, Fabienne Charles

AU - Birkenmeier, Edward H.

AU - King, David S.

AU - Rowe, Lucy B.

AU - McKnight, Steven L.

PY - 1994

Y1 - 1994

N2 - 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 GABPβ 1-1 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-tenninal 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.

AB - 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 GABPβ 1-1 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-tenninal 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.

KW - α-helical

KW - Coiled-coil

KW - Dimerization

KW - Gabpβ

KW - Gene expression

KW - Transcription complexes

UR - http://www.scopus.com/inward/record.url?scp=0028129389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028129389&partnerID=8YFLogxK

M3 - Article

C2 - 7958862

AN - SCOPUS:0028129389

VL - 8

SP - 1853

EP - 1865

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 15

ER -