The shedding protease ADAM17: Physiology and pathophysiology

Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2059-2070. doi: 10.1016/j.bbamcr.2017.07.001. Epub 2017 Jul 11.


The disintegrin metalloprotease ADAM17 has been a matter of intense studies aiming to unravel structure, function and regulation of protease expression, maturation and activity. In this review, we summarize data on the physiological role of ADAM17 in health and disease. Here we provide an overview of ADAM17 substrates, mouse models of ADAM17-deficiencies and discuss recent findings of ADAM17 function in the immune system and central nervous system as well as in cancer. Whereas ADAM17 function in EGF-R-, in Interleukin-6 (IL-6)- and in TNFα-biology has been shown to play a decisive role in regulation of the immune system as well as cancer development, the role of ADAM17 in the central nervous system and neurodegeneration still remains elusive. We show ADAM17 expression in human dopaminergic neurons derived from induced pluripotent stem cells and we discuss how this state-of-the-art technology can be further exploited to study the function of this important protease in the brain and other tissues. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.

Keywords: ADAM proteases; ADAM17; EGF receptor; IL-6 trans-signaling; IL-6R; Shedding; iPS cell system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADAM17 Protein / deficiency*
  • ADAM17 Protein / genetics*
  • ADAM17 Protein / metabolism
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / pathology
  • ErbB Receptors / genetics
  • Humans
  • Immune System / metabolism
  • Immune System / pathology
  • Interleukin-6 / genetics
  • Mice
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Substrate Specificity
  • Tumor Necrosis Factor-alpha / genetics


  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • EGFR protein, human
  • ErbB Receptors
  • ADAM17 Protein
  • ADAM17 protein, human