Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis.

ABSTRACT: Tumor necrosis factor alpha (TNF-?) plays a role in apoptosis and proliferation in multiple types of cells, and defects in TNF-?-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-?-induced apoptosis. Trim27-deficient mice are resistant to TNF-?-d-galactosamine-induced hepatocyte apoptosis. Trim27-deficient mouse embryonic fibroblasts (MEFs) are also resistant to TNF-?-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-?-induced apoptosis. Our findings indicate that the ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-?-induced apoptosis.

SUBMITTER: Zaman MM 

PROVIDER: S-EPMC3889550 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature