The secretases that cleave angiotensin converting enzyme and the amyloid precursor protein are distinct from tumour necrosis factor‐α convertase

Abstract

Angiotensin converting enzyme (ACE) and the Alzheimer's amyloid precursor protein are cleaved from the membrane by zinc metalloproteinases termed ACE secretase and α-secretase, respectively. Tumour necrosis factor-α (TNF-α) convertase (ADAM 17) is a recently identified member of the adamalysin family of mammalian zinc metalloproteinases that is involved in the production of TNF-α and possibly in the cleavage of other membrane proteins. Using two different cell-free assays we were unable to detect significant cleavage and secretion of ACE by TNF-α convertase. In addition, there was a different effect of three hydroxamic acid-based inhibitors (batimastat, compound 1 and compound 4) towards TNF-α convertase as compared to ACE secretase and α-secretase. Thus TNF-α convertase would appear to be distinct from, but possibly related to, the secretases that cleave ACE and the amyloid precursor protein.