title: SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation.
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.
authors: 1] Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier, UMR 5535, CNRS, Montpellier, France [2] Université Montpellier 2, Place Eugène Bataillon, Montpellier, France [3] Université Montpellier 1, 5 Bd Henri IV, Montpellier, France.
authors: D
authors: D
authors: Tempé
authors: 1] IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France [2] Université Montpellier 1, INSERM U896, Montpellier, France [3] CRLC Val d'Aurelle Paul Lamarque, Montpellier, France.
authors: E
authors: E
authors: Vives
authors: 1] Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier, UMR 5535, CNRS, Montpellier, France [2] Université Montpellier 2, Place Eugène Bataillon, Montpellier, France [3] Université Montpellier 1, 5 Bd Henri IV, Montpellier, France.
authors: F
authors: F
authors: Brockly
authors: 1] Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier, UMR 5535, CNRS, Montpellier, France [2] Université Montpellier 2, Place Eugène Bataillon, Montpellier, France [3] Université Montpellier 1, 5 Bd Henri IV, Montpellier, France.
authors: H
authors: H
authors: Brooks
authors: Montpellier RIO Imaging, BIOCAMPUS Montpellier, 141, rue de la cardonille, Montpellier, France.
authors: S
authors: S
authors: De Rossi
authors: 1] Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier, UMR 5535, CNRS, Montpellier, France [2] Université Montpellier 2, Place Eugène Bataillon, Montpellier, France [3] Université Montpellier 1, 5 Bd Henri IV, Montpellier, France.
authors: M
authors: M
authors: Piechaczyk
authors: 1] Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier, UMR 5535, CNRS, Montpellier, France [2] Université Montpellier 2, Place Eugène Bataillon, Montpellier, France [3] Université Montpellier 1, 5 Bd Henri IV, Montpellier, France.
authors: G
authors: G
authors: Bossis
mesh_terms: D001483:Base Sequence; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D012319:RNA Polymerase II