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

Abstract

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.

• Authors: Dhanendra Tomar, Rajesh Singh
• Journal: Cellular signalling (Cell Signal) Vol. 26 Issue 12 Pg. 2606-13 (Dec 2014) ISSN: 1873-3913 [Electronic] England
• PMID: 25152375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• IKBKG protein, human
• NF-kappa B
• TRIM13 protein, human
• Tumor Necrosis Factor-alpha
• Tumor Suppressor Proteins
• Ubiquitin-Protein Ligases
• I-kappa B Kinase

Topics

• Autophagy (physiology)
• Cell Line
• Cell Line, Tumor
• DNA-Binding Proteins (metabolism)
• Endoplasmic Reticulum (metabolism)
• Gene Expression Regulation
• HEK293 Cells
• HeLa Cells
• Humans
• I-kappa B Kinase (metabolism)
• MCF-7 Cells
• NF-kappa B (metabolism)
• Protein Processing, Post-Translational (physiology)
• Signal Transduction (physiology)
• Tumor Necrosis Factor-alpha (metabolism)
• Tumor Suppressor Proteins (metabolism)
• Ubiquitin-Protein Ligases (metabolism)
• Ubiquitination (physiology)