Participation of the E3-ligase TRIM13 in NF-κB p65 activation and NFAT-dependent activation of c-Rel upon T-cell receptor engagement.
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.
['Hatchi|Emeline M|EM|', 'Poalas|Konstantinos|K|', 'Cordeiro|Nelia|N|', "N'Debi|Mélissa|M|", 'Gavard|Julie|J|', 'Bidère|Nicolas|N|']
D015153:Blotting, Western D002467:Cell Nucleus D002478:Cells, Cultured D004268:DNA-Binding Proteins D005786:Gene Expression Regulation D006801:Humans D047468:Immunoprecipitation D008213:Lymphocyte Activation D016328:NF-kappa B D050778:NFATC Transcription Factors D011401:Promoter Regions, Genetic D020569:Proto-Oncogene Proteins c-rel D011948:Receptors, Antigen, T-Cell D015398:Signal Transduction D013601:T-Lymphocytes D051996:Transcription Factor RelA D025521:Tumor Suppressor Proteins
NF-κB Lymphocytes Ubiquitylation Signaling