Jun and Fos heterodimerize with ATFa, a member of the ATF/CREB family and modulate its transcriptional activity.
Three related clones encoding proteins (ATFa1, 2 and 3) with specific ATF/CRE DNA-binding activities have been isolated from HeLa cell cDNA libraries. All three isoforms have weak effects on the basal activity of the adenovirus E2a promoter. We present evidence suggesting that a C-terminal element of the ATFa molecules negatively interferes with the intrinsic activation function of these proteins. We also show that coexpression of ATFa with c-Jun, Jun-B or Jun-D stimulates ATFa-dependent reporter activity, while coexpression of c-Fos has no effect. Deletion analyses indicate that the metal-binding region of ATFa is dispensible for this effect, but that the domain comprising the leucine-zipper region of ATFa is required. Reciprocal co-immunoprecipitation experiments and electrophoretic band-shift assays with in vitro synthesized proteins reveal direct interactions between ATFa and Jun or Fos. The ATFa/c-Jun heterodimers, but not the ATFa/c-Fos complexes, bind efficiently to ATF, CRE or AP1 sites. The detection of ATFa-Jun complexes in crude extracts from HeLa cells transfected with ATFa and c-Jun expression vectors suggests that such ATFa/c-Jun heterodimers also form in vivo. Altogether these results indicate that the ATFa proteins may contribute to the modulation of the activity of the Jun/Fos complexes by altering their DNA-binding and transcriptional properties.
Chatton
B
B
Laboratoire de Génétique Moléculaire des Eucaryotes (CNRS), Unité 184 (INSERM), Institut de Chimie Biologique, Strasbourg, France.
Bocco
J L
JL
Goetz
J
J
Gaire
M
M
Lutz
Y
Y
Kedinger
C
C
D051696:Activating Transcription Factors; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007536:Isomerism; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection
D051696:Activating Transcription Factors; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D004247:DNA