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.