Generation and degradation of human endostatin proteins by various proteinases.
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.
Ferreras
M
M
OSTEOPRO and Center for Clinical and Basic Research Herlev/Ballerup, Herlev, Denmark. mf@osteopro.dk
Felbor
U
U
Lenhard
T
T
Olsen
B R
BR
Delaissé
J
J
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D002460:Cell Line; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D043170:Collagen Type XVIII; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D043169:Endostatins; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020539:Sequence Analysis, Protein; D012697:Serine Endopeptidases / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003094:Collagen; D002403:Cathepsins; D010450:Endopeptidases; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D; D020782:Matrix Metalloproteinases