A brief history of tumor necrosis factor α - converting enzyme: An overview of ectodomain shedding

Keisuke Horiuchi

Research output: Contribution to journalReview article

23 Citations (Scopus)


Many membrane-bound molecules are cleaved at the cell surface, thereby releasing their extracellular domains. This process, often referred to as ectodomain shedding, has emerged as a critical post-translational mechanism for various membrane-bound ligands, receptors, and adhesion molecules. Tumor necrosis factor α (TNFα)-converting enzyme (TACE/ADAM17) was originally identified as an enzyme responsible for releasing the membrane-bound TNFα precursor. However, subsequent studies found an exceptionally large number of target molecules of TACE, including the ligands for epidermal growth factor receptor, L-selectin, CD44, and vascular growth factor receptor 2. Furthermore, in vivo studies using TACE-conditional knockout mice demonstrated the crucial roles of TACE and ectodomain shedding under both physiological and pathological conditions. However, the potential clinical application of the manipulation of TACE activity remains to be investigated.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalKeio Journal of Medicine
Issue number1
Publication statusPublished - 2013 Mar



  • Ectodomain shedding
  • TNFα

ASJC Scopus subject areas

  • Medicine(all)

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