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Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis
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.
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Bergers, G., Javaherian, K., Lo, K.-M., Folkman, J., & Hanahan, D. (1999) · Science · doi:10.1126/science.284.5415.808 · Cited by 988
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Metadata
- Authors
- Maeshima, Y., Sudhakar, A., Lively, J. C., Ueki, K., Kharbanda, S., Kahn, C. R., Sonenberg, N., Hynes, R. O., & Kalluri, R.
- Venue
- Science
- Published
- 2002-01-04
- Volume
- 295
- Issue
- 5552
- Pages
- 140-143
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1975673533
- Cited by
- 438
- References
- 2
- FWCI
- 16.09
- Type
- journal article
- Language
- en
- Open access
- closed
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- Maeshima, Y., Sudhakar, A., Lively, J. C., Ueki, K., Kharbanda, S., Kahn, C. R., Sonenberg, N., Hynes, R. O., & Kalluri, R. (2002). Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis. Science. https://doi.org/10.1126/science.1065298
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