The secretases that cleave angiotensin converting enzyme and the amyloid precursor protein are distinct from tumour necrosis factor-alpha convertase.
Angiotensin converting enzyme (ACE) and the Alzheimer's amyloid precursor protein are cleaved from the membrane by zinc metalloproteinases termed ACE secretase and alpha-secretase, respectively. Tumour necrosis factor-alpha (TNF-alpha) convertase (ADAM 17) is a recently identified member of the adamalysin family of mammalian zinc metalloproteinases that is involved in the production of TNF-alpha 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-alpha convertase. In addition, there was a different effect of three hydroxamic acid-based inhibitors (batimastat, compound 1 and compound 4) towards TNF-alpha convertase as compared to ACE secretase and alpha-secretase. Thus TNF-alpha convertase would appear to be distinct from, but possibly related to, the secretases that cleave ACE and the amyloid precursor protein.
School of Biochemistry and Molecular Biology, University of Leeds, UK.
S
S
Parvathy
E H
EH
Karran
A J
AJ
Turner
N M
NM
Hooper
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002474:Cell-Free System; D010450:Endopeptidases / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D014409:Tumor Necrosis Factor-alpha; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein