Generation and degradation of human endostatin proteins by various proteinases

• Published in: FEBS letters 2000-12, Vol.486 (3), p.247-251
• Main Authors: Ferreras, Mercedes, Felbor, Ute, Lenhard, Thomas, Olsen, Bjorn R., Delaissé, Jean-Marie
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - metabolism; Aspartic Acid Endopeptidases - metabolism; Cathepsin B - metabolism; Cathepsin D - metabolism; Cathepsin K; Cathepsin L; Cathepsins - metabolism; Cell Line; Collagen - chemistry; Collagen - metabolism; Collagen Type XVIII; Collagen XVIII; Cysteine Endopeptidases - metabolism; DTT, dithiothreitol; Electrophoresis, Polyacrylamide Gel; Endopeptidases - metabolism; Endostatin; Endostatins; hES, human endostatin; hNC1, human NC1; Humans; Matrix Metalloproteinases - metabolism; MMP, matrix metalloproteinase; mNC1, murine NC1; NC1; Peptide Fragments - analysis; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Structure, Tertiary; Proteinase; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Analysis, Protein; Serine Endopeptidases - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)02249-3

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.