title: 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.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, India.
authors.forename: Dhanendra
authors.initials: D
authors.lastname: Tomar
authors.affiliation: Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, India. Electronic address: singhraj1975@gmail.com.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
mesh_terms: D001343:Autophagy / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C491731:IKBKG protein, human; D016328:NF-kappa B; C112217:TRIM13 protein, human; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051550:I-kappa B Kinase
keywords: Clonogenic ability; NEMO; NF-κB; TNF; TRIM13; Tumor suppressor