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Oncogene. 1994 Feb;9(2):375-85.

Jun and Fos heterodimerize with ATFa, a member of the ATF/CREB family and modulate its transcriptional activity.

Author information

1
Laboratoire de Génétique Moléculaire des Eucaryotes (CNRS), Unité 184 (INSERM), Institut de Chimie Biologique, Strasbourg, France.

Abstract

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.

PMID:
8290251
[Indexed for MEDLINE]

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