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.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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Carcinoma, Squamous Cell / enzymology
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Carcinoma, Squamous Cell / metabolism*
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Cell Line, Tumor
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Down-Regulation
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Gene Silencing
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HEK293 Cells
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Head and Neck Neoplasms / enzymology
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Head and Neck Neoplasms / metabolism*
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Humans
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Immunoprecipitation
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Lysine / metabolism
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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RNA, Messenger / metabolism
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RNA, Small Interfering
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Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
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Recombinant Fusion Proteins / antagonists & inhibitors
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Squamous Cell Carcinoma of Head and Neck
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Tumor Necrosis Factor-alpha / metabolism*
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Ubiquitin Thiolesterase / antagonists & inhibitors
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Ubiquitin Thiolesterase / genetics
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Ubiquitin Thiolesterase / metabolism*
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Ubiquitin-Specific Proteases
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Ubiquitinated Proteins / metabolism*
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Ubiquitination
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Up-Regulation
Substances
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Neoplasm Proteins
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RNA, Messenger
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Recombinant Proteins
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TNF protein, human
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Tumor Necrosis Factor-alpha
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USP4 protein, human
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Ubiquitinated Proteins
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RIPK1 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinases
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Proteases
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Lysine