Journal
FEBS LETTERS
Volume 486, Issue 3, Pages 247-251Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(00)02249-3
Keywords
endostatin; NCl; collagen XVIII; proteinase; angiogenesis
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The angiogenesis inhibitor endostatin is a fragment of the NC1 domain of collagen XVIII. The generation of endostatin has been investigated only in murine hemangioendothelioma cell cultures and was ascribed to cathepsin L. Distinct endostatin-like fragments were detected in human tissues and serum. To identify proteinases able to generate such fragments, we incubated human NC1 with proteinases of all classes, including cathepsin L. Eleven out of 12 generate fragments with an N-terminus within the same 15 residue stretch as those occurring physiologically, indicating that this region is sensitive to many proteinases. None correspond to mouse endostatin. However, the efficiencies of these proteinases differed markedly. Some proteinases also proved to degrade endostatin, pointing to another regulatory loop of angiogenesis. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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