title: A brief history of tumor necrosis factor α--converting enzyme: an overview of ectodomain shedding.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan. horiuchi@z3.keio.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D008024:Ligands; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; C061153:tumor necrosis factor precursor; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse