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.
Parvathy
S
S
School of Biochemistry and Molecular Biology, University of Leeds, UK.
Karran
E H
EH
Turner
A J
AJ
Hooper
N M
NM
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