{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:23:20Z","timestamp":1772162600761,"version":"3.50.1"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5552","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,1,4]]},"abstract":"<jats:p>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\u2013specific inhibitor of protein synthesis. Through a requisite interaction with \u03b1V\u03b23 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.<\/jats:p>","DOI":"10.1126\/science.1065298","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:47:15Z","timestamp":1027748835000},"page":"140-143","source":"Crossref","is-referenced-by-count":352,"title":["Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis"],"prefix":"10.1126","volume":"295","author":[{"given":"Yohei","family":"Maeshima","sequence":"first","affiliation":[{"name":"Program in Matrix Biology, Department of Medicine and the Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA."}]},{"given":"Akulapalli","family":"Sudhakar","sequence":"additional","affiliation":[{"name":"Program in Matrix Biology, Department of Medicine and the Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA."}]},{"given":"Julie C.","family":"Lively","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]},{"given":"Kohjiro","family":"Ueki","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center and Harvard Medical School,"}]},{"given":"Surender","family":"Kharbanda","sequence":"additional","affiliation":[{"name":"Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA."}]},{"given":"C. Ronald","family":"Kahn","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center and Harvard Medical School,"}]},{"given":"Nahum","family":"Sonenberg","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada H3G 1V6."}]},{"given":"Richard O.","family":"Hynes","sequence":"additional","affiliation":[{"name":"Department of Biology, Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"Program in Matrix Biology, Department of Medicine and the Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA."}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/0955-0674(93)90077-4","volume":"5","author":"McBratney S.","year":"1993","unstructured":"McBratney S., Chen C. 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T3 peptide (LQRFTTMPFLFCNVNDVCNF) T7 peptide (TMPFLFCNVNDVCNFASRNDYSYWL) consisting of residues 69 to 88 and 74 to 98 of tumstatin respectively and mutant T7 peptide (TMPF M FCN I N N VCNFASRNDYSYWL) were synthesized as in (6 8)."},{"key":"e_1_3_1_12_2","unstructured":"Supplemental material is available on Science Online at www.sciencemag.org\/cgi\/content\/full\/295\/5552\/140\/DC1."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/j.1460-2075.1996.tb00398.x","volume":"15","author":"Beretta L.","year":"1996","unstructured":"Beretta L., Gingras A. C., Svitkin Y. V., Hall M. N., Sonenberg N., EMBO J. 15, 658 (1996).","journal-title":"EMBO J."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","unstructured":"M. S. O'Reilly et al. 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