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© Research
Publication : Molecular and cellular biology

Promoter specificity and biological activity of tethered AP-1 dimers

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular and cellular biology - 01 Jul 2002

Bakiri L, Matsuo K, Wisniewska M, Wagner EF, Yaniv M

Link to Pubmed [PMID] – 12052899

Mol. Cell. Biol. 2002 Jul;22(13):4952-64

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 tethered dimer Fra2, but not c-Jun tethered dimer Fra1 and c-Jun tethered dimer cFos (the tilde indicates a tethered dimer), inhibited G(0) 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.

http://www.ncbi.nlm.nih.gov/pubmed/12052899