Angiostatin

From Wikipedia, the free encyclopedia

Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor (i.e., it blocks the growth of new blood vessels), and it is currently underlying clinical trials for its use in anticancer therapy[1].

[edit] Structure

Angiostatin is a 57 kDa fragment of a larger protein, plasmin (itself a fragment of plasminogen) enclosing three to five contiguous Kringle modules. Each module contains two small beta sheets and three disulfide bonds.

[edit] Generation

Angiostatin is produced, for example, by autoproteolytic cleavage of plasminogen, involving extracellular disulfide bond reduction by phosphoglycerate kinase. Furthermore angiostatin can be cleaved from plasminogen by different metalloproteinases (MMPs), elastase, prostata-specific antigen (PSA), 13 KD serine protease, or 24KD endopeptidase.

[edit] Biological activity

Angiostatin is known to bind a lot of proteins, especially to angiomotin and endothelial cell surface ATP synthase but also integrins, annexin II, C-met receptor, NG2-proteoglycans, tissue-type plasminogen activator, chondroitin sulfate proteoglycans, and CD26. Also smaller fragments of angiostatin has been shown to bind several other proteins. There is still considerable uncertainty on its mechanism of action, but it seems to involve for example inhibition of endothelial cell migration, proliferation and induction of apoptosis.