title: Participation of the E3-ligase TRIM13 in NF-κB p65 activation and NFAT-dependent activation of c-Rel upon T-cell receptor engagement.
abstract: The nuclear factor κB (NF-κB) family members p65 and c-Rel chiefly orchestrate lymphocytes activation following T-cell receptor (TCR) engagement. In contrast to p65, which is rapidly mobilized, c-Rel activation occurs subsequently as it involves a nuclear factor of activated T-cells (NFAT)-dependent upregulation step. However, how TCR ligation drives p65 and c-Rel activation is not fully understood. Because several ubiquitylated components of NF-κB signaling cascade accumulate in close proximity to membranes, we screened a siRNA library against E3-ligases that contain transmembrane domains on TCR-mediated NF-κB activation. Here, we report the identification of the endoplasmic reticulum resident TRIM13 protein as an enhancer of NF-κB promoter activity. We found that knocking down TRIM13 by RNA interference reduced the activation of p65, while the translocation of c-Rel into the nucleus was blunted. We further observed that c-Rel induction was diminished without TRIM13, as NFAT activation was compromised. These results unveil that TRIM13 is a selective regulator of p65 and of c-Rel activation.
authors.affiliation: INSERM, UMR_S 1014, Hôpital Paul Brousse, Villejuif 94800, France; Université Paris-Sud P11, Orsay 91400, France; Equipe Labellisée Ligue contre le Cancer, Villejuif, France.
authors.forename: Emeline M
authors.initials: EM
authors.lastname: Hatchi
authors.affiliation: INSERM, UMR_S 1014, Hôpital Paul Brousse, Villejuif 94800, France; Université Paris-Sud P11, Orsay 91400, France; Equipe Labellisée Ligue contre le Cancer, Villejuif, France.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Poalas
authors.affiliation: INSERM, UMR_S 1014, Hôpital Paul Brousse, Villejuif 94800, France; Université Paris-Sud P11, Orsay 91400, France; Equipe Labellisée Ligue contre le Cancer, Villejuif, France.
authors.forename: Nelia
authors.initials: N
authors.lastname: Cordeiro
authors.affiliation: INSERM, UMR_S 1014, Hôpital Paul Brousse, Villejuif 94800, France; Université Paris-Sud P11, Orsay 91400, France; Equipe Labellisée Ligue contre le Cancer, Villejuif, France.
authors.forename: Mélissa
authors.initials: M
authors.lastname: N'Debi
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cite, 6 rue de l'Ecole de Medecine, Paris 75006, France; INSERM, U1016, 22 rue Méchain, Paris 75014, France; CNRS, UMR8104, 22 rue Méchain, Paris 75014, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Gavard
authors.affiliation: INSERM, UMR_S 1014, Hôpital Paul Brousse, Villejuif 94800, France; Université Paris-Sud P11, Orsay 91400, France; Equipe Labellisée Ligue contre le Cancer, Villejuif, France. Electronic address: nicolas.bidere@inserm.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bidère
mesh_terms: D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D020569:Proto-Oncogene Proteins c-rel; D011948:Receptors, Antigen, T-Cell; C112217:TRIM13 protein, human; D051996:Transcription Factor RelA; D025521:Tumor Suppressor Proteins
keywords: Lymphocytes; NF-κB; Signaling; Ubiquitylation