Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis.
Tumor necrosis factor alpha (TNF-α) plays a role in apoptosis and proliferation in multiple types of cells, and defects in TNF-α-induced apoptosis are associated with various autoimmune diseases. Here, we show that TRIM27, a tripartite motif (TRIM) protein containing RING finger, B-box, and coiled-coil domains, positively regulates TNF-α-induced apoptosis. Trim27-deficient ... mice are resistant to TNF-α-d-galactosamine-induced hepatocyte apoptosis. Trim27-deficient mouse embryonic fibroblasts (MEFs) are also resistant to TNF-α-cycloheximide-induced apoptosis. TRIM27 forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which deubiquitinates receptor-interacting protein 1 (RIP1), resulting in the positive regulation of TNF-α-induced apoptosis. Our findings indicate that the ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-α-induced apoptosis.
Mesh Terms:
Animals, Apoptosis, Cycloheximide, DNA-Binding Proteins, Fibroblasts, GTPase-Activating Proteins, HEK293 Cells, Hep G2 Cells, Hepatocytes, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Nuclear Proteins, Polyubiquitin, Protein Multimerization, Protein Synthesis Inhibitors, Protein Transport, Tumor Necrosis Factor-alpha, Ubiquitin-Specific Proteases, Ubiquitination
Animals, Apoptosis, Cycloheximide, DNA-Binding Proteins, Fibroblasts, GTPase-Activating Proteins, HEK293 Cells, Hep G2 Cells, Hepatocytes, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Nuclear Proteins, Polyubiquitin, Protein Multimerization, Protein Synthesis Inhibitors, Protein Transport, Tumor Necrosis Factor-alpha, Ubiquitin-Specific Proteases, Ubiquitination
Mol. Cell. Biol.
Date: Dec. 01, 2013
PubMed ID: 24144979
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