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GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription.

Publication ,  Journal Article
Rosmarin, AG; Caprio, DG; Kirsch, DG; Handa, H; Simkevich, CP
Published in: J Biol Chem
October 6, 1995

CD18 (beta 2 leukocyte integrin) is a leukocyte-specific adhesion molecule that plays a crucial role in immune and inflammatory responses. A 79-nucleotide fragment of the CD18 promoter is sufficient to direct myeloid transcription. The CD18 promoter is bound by the B lymphocyte- and myeloid-restricted ets factor, PU.1, and disruption of the PU.1-binding sites significantly reduces promoter activity. However, PU.1 alone cannot fully account for the leukocyte-specific and myeloid-inducible transcription of CD18. We identified a ubiquitously expressed nuclear protein complex of extremely low electrophoretic mobility that also binds to this region of the CD18 promoter. This binding complex is a heterotetramer composed of GABP alpha, and ets factor, and GABP beta, a subunit with homology to Drosophila Notch. GABP alpha competes with the lineage restricted factor, PU.1, for the same critical CD18 ets sites. The CD18 promoter is activated in myeloid cells by transfection with both GABP alpha and GABP beta together, but not by either factor alone. Transfection of non-hematopoietic cells with the two GABP subunits together with PU.1 is sufficient to activate CD18 transcription in otherwise non-permissive cells. Thus, GABP and PU.1 compete for the same binding sites but cooperate to activate CD18 transcription.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 6, 1995

Volume

270

Issue

40

Start / End Page

23627 / 23633

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Retroviridae Proteins, Oncogenic
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Humans
  • GA-Binding Protein Transcription Factor
 

Citation

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Rosmarin, A. G., Caprio, D. G., Kirsch, D. G., Handa, H., & Simkevich, C. P. (1995). GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription. J Biol Chem, 270(40), 23627–23633. https://doi.org/10.1074/jbc.270.40.23627
Rosmarin, A. G., D. G. Caprio, D. G. Kirsch, H. Handa, and C. P. Simkevich. “GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription.J Biol Chem 270, no. 40 (October 6, 1995): 23627–33. https://doi.org/10.1074/jbc.270.40.23627.
Rosmarin AG, Caprio DG, Kirsch DG, Handa H, Simkevich CP. GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription. J Biol Chem. 1995 Oct 6;270(40):23627–33.
Rosmarin, A. G., et al. “GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription.J Biol Chem, vol. 270, no. 40, Oct. 1995, pp. 23627–33. Pubmed, doi:10.1074/jbc.270.40.23627.
Rosmarin AG, Caprio DG, Kirsch DG, Handa H, Simkevich CP. GABP and PU.1 compete for binding, yet cooperate to increase CD18 (beta 2 leukocyte integrin) transcription. J Biol Chem. 1995 Oct 6;270(40):23627–23633.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 6, 1995

Volume

270

Issue

40

Start / End Page

23627 / 23633

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Retroviridae Proteins, Oncogenic
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Humans
  • GA-Binding Protein Transcription Factor