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

FEBS Lett. 1998 Jul 10;431(1):63-5. doi: 10.1016/s0014-5793(98)00726-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • ADAM17 Protein
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Cell-Free System
  • Endopeptidases / metabolism*
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / metabolism*
  • Peptidyl-Dipeptidase A / metabolism*
  • Swine
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Amyloid beta-Protein Precursor
  • Tumor Necrosis Factor-alpha
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Peptidyl-Dipeptidase A
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAM17 Protein