Specificities of protein-protein and protein-DNA interaction of GABPα and two newly defined ets-related proteins

Thomas A. Brown, Steven L. McKnight

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

The ets-related protein GABPα interacts with the four ankyrin-type (ANK) repeats of GABPβ to form a high-affinity DNA-binding complex that recognizes a site important for herpes simplex virus type I immediate early gene activation. To investigate the selectivity and specificity of the GABP complex, we have isolated two new ETS family members, termed ER81 and ER71. ER81 and GABPα were present in most tissues of adult mice, whereas ER71 was restricted to testis. We have compared the DNA-binding specificities of these proteins by binding site selection. GABPα, ER71, and ER81 recognized the common pentanucleotide DNA seauence 5′-CGGAA/T-3′. Although subtle differences were observed for nucleotide preferences flanking this pentanucleotide core, the overall similarity of the selected sequences was most striking. Given the observation that GABPα interaction with GABPβ requires its intact ETS domain we further compared the ability of GABPβ to interact with other ETS proteins. GABPβ did not augment the DNA-binding activity of the highly similar ETS domains of ER81, ER71, or Ets-1. Moreover, probing of total tissue extracts with radiolabeled GABPβ demonstrated its exceedingly stringent specificity for GABPα. Given that the DNA-binding specificities of these ETS proteins are similar and that the protein-protein interactions between GABPβ and GABPα are highly specific, we conclude that the protein interactions determine the target site selection by GABPα.

Original languageEnglish (US)
Pages (from-to)2502-2512
Number of pages11
JournalGenes and Development
Volume6
Issue number12 PART B
StatePublished - Dec 1992

Fingerprint

DNA
Proteins
Ankyrin Repeat
Immediate-Early Genes
Aptitude
Tissue Extracts
DNA-Binding Proteins
Simplexvirus
Protein Binding
Transcriptional Activation
Testis
Nucleotides
Binding Sites
ETS Motif

Keywords

  • Ankyrin repeats
  • DNA-binding protein
  • Ets
  • ETS domain
  • Notch
  • Testis
  • Transcription factor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Specificities of protein-protein and protein-DNA interaction of GABPα and two newly defined ets-related proteins. / Brown, Thomas A.; McKnight, Steven L.

In: Genes and Development, Vol. 6, No. 12 PART B, 12.1992, p. 2502-2512.

Research output: Contribution to journalArticle

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