title: Ubiquitin-specific protease 4 promotes TNF-α-induced apoptosis by deubiquitination of RIP1 in head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer. Better understanding of molecular aberrations associated with HNSCC might identify new diagnostic and therapeutic strategies for this disease. In this study, we found ubiquitin-specific protease 4 (USP4) was significantly upregulated in HNSCC. USP4 negatively regulates RIP1-mediated NF-κB activation and promotes TNF-α-induced apoptosis in FaDu cells. USP4 directly interacts with receptor-interacting protein 1 (RIP1) and deubiquitinates K63-linked ubiquitination from RIP1. Therefore, our results indicate that USP4 has tumor suppressor roles in HNSCC and suggest USP4 as a potential therapeutic target for HNSCC.
authors: Department of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
authors: Xiaozhi
authors: X
authors: Hou
authors: Lijuan
authors: L
authors: Wang
authors: Lei
authors: L
authors: Zhang
authors: Xinliang
authors: X
authors: Pan
authors: Wei
authors: W
authors: Zhao
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020868:Gene Silencing; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases; D057149:Ubiquitinated Proteins / Q000378:metabolism*; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C486203:USP4 protein, human; D057149:Ubiquitinated Proteins; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D008239:Lysine