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SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation

Oncogene volume 33, pages 921–927 (2014)Cite this article

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Abstract

The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153, an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

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Acknowledgements

We are grateful to Drs R Hipskind, I Jariel-Encontre, T Salem and G Moquet-Torcy for fruitful discussions and critical reading of the manuscript. MP’s laboratory is an ‘Equipe Labellisée’ of the French Ligue Nationale contre le Cancer. This work was also supported by the CNRS, the Association pour la Recherche sur le Cancer (ARC), and the Agence Nationale de la Recherche (BLAN08-3_310119).

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Author notes

  1. H Brooks

    Present address: 8Present address: Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Center, UNSW, PO Box 81, Randwick, NSW 2031, Australia.,

  2. M Piechaczyk and G Bossis: These authors contributed equally to this work.

Authors and Affiliations

  1. Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier, UMR 5535, CNRS, Montpellier, France

    D Tempé, F Brockly, H Brooks, M Piechaczyk & G Bossis

  2. Université Montpellier 2, Place Eugène Bataillon, Montpellier, France

    D Tempé, F Brockly, H Brooks, M Piechaczyk & G Bossis

  3. Université Montpellier 1, 5 Bd Henri IV, Montpellier, France

    D Tempé, F Brockly, H Brooks, M Piechaczyk & G Bossis

  4. IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France

    E Vives

  5. Université Montpellier 1, INSERM U896, Montpellier, France

    E Vives

  6. CRLC Val d’Aurelle Paul Lamarque, Montpellier, France

    E Vives

  7. Montpellier RIO Imaging, BIOCAMPUS Montpellier, 141, rue de la cardonille, Montpellier, France

    S De Rossi

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  1. D Tempé
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Correspondence to G Bossis.

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Tempé, D., Vives, E., Brockly, F. et al. SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation. Oncogene 33, 921–927 (2014). https://doi.org/10.1038/onc.2013.4

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