Participation of the E3-ligase TRIM13 in NF-κB p65 activation and NFAT-dependent activation of c-Rel upon T-cell receptor engagement

• Published in: The international journal of biochemistry & cell biology Vol. 54; pp. 217 - 222
• Main Authors: Hatchi, Emeline M., Poalas, Konstantinos, Cordeiro, Nelia, N’Debi, Mélissa, Gavard, Julie, Bidère, Nicolas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-09-2014
• Subjects: Blotting, Western; Cell Nucleus - metabolism; Cells, Cultured; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Humans; Immunoprecipitation; Lymphocyte Activation; Lymphocytes; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins c-rel - antagonists & inhibitors; Proto-Oncogene Proteins c-rel - genetics; Proto-Oncogene Proteins c-rel - metabolism; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; Signaling; T-Lymphocytes - metabolism; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Tumor Suppressor Proteins - antagonists & inhibitors; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Ubiquitylation; NF-κB; Signaling; Lymphocytes; Ubiquitylation
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2014.07.012

•TRIM13 participates to NF-κB signaling upon T-cell receptor engagement.•TRIM13 controls c-Rel activation via NFAT.•TRIM13 knockdown reduces NF-κB p65 nuclear maintenance.
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.