Ubiquitin-specific protease 4 promotes TNF-α-induced apoptosis by deubiquitination of RIP1 in head and neck squamous cell carcinoma

FEBS Lett. 2013 Feb 14;587(4):311-6. doi: 10.1016/j.febslet.2012.12.016. Epub 2013 Jan 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Silencing
  • HEK293 Cells
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Immunoprecipitation
  • Lysine / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Necrosis Factor-alpha / metabolism*
  • Ubiquitin Thiolesterase / antagonists & inhibitors
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitin-Specific Proteases
  • Ubiquitinated Proteins / metabolism*
  • Ubiquitination
  • Up-Regulation

Substances

  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • USP4 protein, human
  • Ubiquitinated Proteins
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases
  • Lysine