title: Nucleo-cytoplasmic trafficking of TRIM8, a novel oncogene, is involved in positive regulation of TNF induced NF-κB pathway.
abstract: TNF induced nuclear factor kappa B (NF-κB) is one of the central signaling pathways that plays a critical role in carcinogenesis and inflammatory diseases. Post-translational modification through ubiquitin plays important role in the regulation of this pathway. In the current study, we investigated the role of TRIM8, member of RING family ubiquitin ligase in regulation of NF-κB pathway. We observed that TRIM8 positively regulates TNF induced NF-κB pathway. Different domains of TRIM8 showed discrete functions at the different steps in regulation of TNF induced NF-κB pathway. Ubiquitin ligase activity of TRIM8 is essential for regulation of NF-κB activation in both cytoplasm as well as nucleus. TRIM8 negates PIAS3 mediated negative repression of NF-κB at p65 by inducing translocation of PIAS3 from nucleus to cytoplasm as well as its turnover. TNF induces translocation of TRIM8 from nucleus to cytoplasm, which positively regulates NF-κB. The cytoplasmic translocation of TRIM8 is essential for TNF induced NF-κB but not for p65 mediated NF-κB regulation. TRIM8 also enhanced the clonogenic and migration ability of cells by modulating NF-κB. The further study will help to understand the role of TRIM8 in inflammation and cancer.
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.forename: Lakshmi
authors.initials: L
authors.lastname: Sripada
authors.forename: Paresh
authors.initials: P
authors.lastname: Prajapati
authors.forename: Rochika
authors.initials: R
authors.lastname: Singh
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Rajesh
authors.initials: R
authors.lastname: Singh
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D020868:Gene Silencing; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D061986:MCF-7 Cells; D018832:Molecular Chaperones / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; C418604:TRIM8 protein, human; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase