Promoter specificity and biological activity of tethered AP-1 dimers

Latifa Bakiri, Koichi Matsuo, Marta Wisniewska, Erwin F. Wagner, Moshe Yaniv

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of Jun, Fos, and ATF family proteins. Both gain- and loss-of-function studies have revealed specific roles for individual AP-1 components in cell proliferation, differentiation, apoptosis, and other biological processes. However, little is known about the functions of specific AP-1 dimers. To test the importance of AP-1 composition in transcriptional activation, AP-1 monomers were joined via a flexible polypeptide tether to force specific pairing. The resultant single-chain AP-1 molecules showed DNA binding specificity and transcriptional activation potentials similar to those of untethered dimers, even in the presence of dominant-negative AP-1 monomers. c-Jun-containing dimers showed distinct promoter specificity in transient-transfection experiments, depending on the Fos, Fra, or ATF partner. When stably expressed in NIH 3T3 cells, c-Jun∼Fra2, but not c-Jun∼Fra1 and c-Jun∼cFos (the tilde indicates a tethered dimer), inhibited G0 arrest at confluency and under low-serum conditions and specifically activated cyclin A expression. These data suggest that the choice of dimerization partner defines the role of c-Jun in gene activation and cell cycle regulation and that single-chain AP-1 molecules provide a powerful tool for assessing the role of specific AP-1 dimers.

Original languageEnglish
Pages (from-to)4952-4964
Number of pages13
JournalMolecular and Cellular Biology
Volume22
Issue number13
DOIs
Publication statusPublished - 2002
Externally publishedYes

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Transcription Factor AP-1
Transcriptional Activation
jun Genes
Activator Appliances
Biological Phenomena
Cyclin A
NIH 3T3 Cells
Dimerization
Transfection
Cell Differentiation
Cell Cycle
Transcription Factors
Cell Proliferation
Apoptosis
Peptides
DNA
Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Promoter specificity and biological activity of tethered AP-1 dimers. / Bakiri, Latifa; Matsuo, Koichi; Wisniewska, Marta; Wagner, Erwin F.; Yaniv, Moshe.

In: Molecular and Cellular Biology, Vol. 22, No. 13, 2002, p. 4952-4964.

Research output: Contribution to journalArticle

Bakiri, Latifa ; Matsuo, Koichi ; Wisniewska, Marta ; Wagner, Erwin F. ; Yaniv, Moshe. / Promoter specificity and biological activity of tethered AP-1 dimers. In: Molecular and Cellular Biology. 2002 ; Vol. 22, No. 13. pp. 4952-4964.
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