TNF-α converting enzyme (TACE) - From the bench to the bedside

Pazit Salamon, Yoseph A. Mekori

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Tumor necrosis factor-α (TNF-α) is a cytokine which has been demonstrated to mediate many crucial events for the initiation of both acute and chronic inflammatory processes. The 26 kDa membrane-bound precursor form of the protein is cleaved from the cell surface by a process termed ectodomain shedding, resulting in a soluble, 17 kDa mature form. The involvement of TNF-α in a variety of inflammatory states prompted researchers to identify the enzyme responsible for TNF-α shedding. TNF-α converting enzyme or TACE, the enzyme that is responsible for TNF-α shedding from the cell membrane, was identified in 1997. TACE is a member of the adamalysin family of zinc-binding metalloproteinases. Analysis of TACE mutant mice has raised the possibility that TACE plays a role in other processes in addition to TNF-α shedding. Methods/Data base: A review of the literature. Results/Conclusions: TACE was first discovered as the enzyme responsible for TNF-α shedding from the cell membrane. It has also been found to participate in the shedding of several other substrates besides TNF-α, including IL-6Rα, L-selectin, and CD40, indicating a possible role in inflammatory processes such as allergic inflammation. Therefore, TACE has become a target for designing inhibitors for therapeutic treatment.

Original languageEnglish
Pages (from-to)30-35
Number of pages6
JournalAllergy and Clinical Immunology International
Volume17
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • ADAM17
  • Inflammation
  • TACE
  • TNF-α
  • Therapeutics

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