TRIM13 regulates ubiquitination and turnover of NEMO to suppress TNF induced NF-κB activation.

The NF-κB family of transcription factors is activated in response to various intracellular or extracellular stimuli and its dysregulation leads to pathological conditions like infection, cancer, neurodegenerative disorders. The post-translational modification by ubiquitination regulates various steps of NF-κB pathway. In the current study, we have described the role of TRIM13, an endoplasmic reticulum (ER) membrane anchored E3 ligase in regulation of NF-κB. The expression of TRIM13 represses TNF induced NF-κB while the knockdown has the opposite effect. The E3 ligase activity and ER localization is essential for NF-κB suppression whereas TRIM13 regulated autophagy is not essential. TRIM13 interacts with NEMO and modulates its ubiquitination and turnover, hence may regulate IKK complex activity. TRIM13 mediated NF-κB repression is essential for negative regulation of clonogenic ability of the cells. This study for the first time demonstrated the role of TRIM13, ER resident RING E3 ligase as a novel regulator of NEMO ubiquitination, negative regulator of NF-κB signaling and its role as a tumor suppressor.