Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis
- 4 January 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 295 (5552), 140-143
- https://doi.org/10.1126/science.1065298
Abstract
Tumstatin is a 28-kilodalton fragment of type IV collagen that displays both anti-angiogenic and proapoptotic activity. Here we show that tumstatin functions as an endothelial cell–specific inhibitor of protein synthesis. Through a requisite interaction with αVβ3 integrin, tumstatin inhibits activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3-kinase), protein kinase B (PKB/Akt), and mammalian target of rapamycin (mTOR), and it prevents the dissociation of eukaryotic initiation factor 4E protein (eIF4E) from 4E-binding protein 1. These results establish a role for integrins in mediating cell-specific inhibition of cap-dependent protein synthesis and suggest a potential mechanism for tumstatin's selective effects on endothelial cells.Keywords
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