Promoter specificity and biological activity of tethered AP-1 dimers.
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.
Bakiri
Latifa
L
Unité Expression Génétique et Maladies, CNRS URA 1644, Institut Pasteur, 75724 Paris Cedex 15, France.
Matsuo
Koichi
K
Wisniewska
Marta
M
Wagner
Erwin F
EF
Yaniv
Moshe
M
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D051921:Fos-Related Antigen-2; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors