title: Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis.
abstract: 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.
authors.affiliation: Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki, Japan.
authors.forename: Mohammad Mahabub-Uz
authors.initials: MM
authors.lastname: Zaman
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nomura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takagi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Okamura
authors.forename: Wanzhu
authors.initials: W
authors.lastname: Jin
authors.forename: Toshie
authors.initials: T
authors.lastname: Shinagawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
mesh_terms: D000818:Animals; D017209:Apoptosis; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism; D055503:Protein Multimerization; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*; D054875:Ubiquitination; D000070584:Tripartite Motif Proteins
chemical_list: D003513:Cycloheximide; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; D025821:Polyubiquitin; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; C490620:Ralbp1 protein, mouse; C489296:Trim27 protein, mouse; D000070584:Tripartite Motif Proteins; C579190:Usp7 protein, mouse