ADAM-17: the enzyme that does it all

Abstract

This review focuses on the role of ADAM-17 in disease. Since its debut as the tumor necrosis factor converting enzyme (TACE), ADAM-17 has been reported to be an indispensible regulator of almost every cellular event from proliferation to migration. The central role of ADAM-17 in cell regulation is rooted in its diverse array of substrates: cytokines, growth factors, and their receptors as well as adhesion molecules are activated or inactivated by their cleavage with ADAM-17. It is therefore not surprising that ADAM-17 is implicated in numerous human diseases including cancer, heart disease, diabetes, rheumatoid arthritis, kidney fibrosis, Alzheimer’s disease, and is a promising target for future treatments. The specific role of ADAM-17 in the pathophysiology of these diseases is very complex and depends on the cellular context. To exploit the therapeutic potential of ADAM-17, it is important to understand how its activity is regulated and how specific organs and cells can be targeted to inactivate or activate the enzyme.

Keywords::

• Ectodomain shedding
• growth factor
• inflammation
• signalling
• proteolysis
• TNFα

Acknowledgements

I am thankful for Dr. Pal Gooz for critical reading of the manuscript and for Dr. Jennifer Schnellmann at the Office of Scientific Editing and Publications at the Medical University of South Carolina for critical reading and editing the manuscript.

Declaration of interest

This work was supported by grants from the National Institutes of Health (NIH/NIDDK K01 DK070054 and NIH/NIDDK ARRA supplement 3K01DK070054-05S1) and from the Paul Teschan Research Fund of the Dialysis Clinic, Inc.

Editor: Michael M. Cox