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Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis

Science  04 Jan 2002:
Vol. 295, Issue 5552, pp. 140-143
DOI: 10.1126/science.1065298

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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.

  • * These authors contributed equally to this work.

  • Present address: Ilex Oncology, Boston, MA 02216, USA.

  • To whom correspondence should be addressed. E-mail: rkalluri{at}caregroup.harvard.edu

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