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dc.contributor.authorTeodoro, Jose G.
dc.contributor.authorParker, Albert E.
dc.contributor.authorZhu, Xiaochun
dc.contributor.authorGreen, Michael R.
dc.date2022-08-11T08:09:35.000
dc.date.accessioned2022-08-23T16:36:26Z
dc.date.available2022-08-23T16:36:26Z
dc.date.issued2006-08-19
dc.date.submitted2009-03-31
dc.identifier.citationScience. 2006 Aug 18;313(5789):968-71. <a href="http://dx.doi.org/10.1126/science.1126391">Link to article on publisher's site</a>
dc.identifier.issn1095-9203 (Electronic)
dc.identifier.doi10.1126/science.1126391
dc.identifier.pmid16917063
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38786
dc.description.abstractRecent evidence suggests that antiangiogenic therapy is sensitive to p53 status in tumors, implicating a role for p53 in the regulation of angiogenesis. Here we show that p53 transcriptionally activates the alpha(II) collagen prolyl-4-hydroxylase [alpha(II)PH] gene, resulting in the extracellular release of antiangiogenic fragments of collagen type 4 and 18. Conditioned media from cells ectopically expressing either p53 or alpha(II)PH selectively inhibited growth of primary human endothelial cells. When expressed intracellularly or exogenously delivered, alpha(II)PH significantly inhibited tumor growth in mice. Our results reveal a genetic and biochemical linkage between the p53 tumor suppressor pathway and the synthesis of antiangiogenic collagen fragments.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16917063&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1126/science.1126391
dc.subject*Angiogenesis Inhibitors
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectAutoantigens
dc.subjectCell Line, Tumor
dc.subjectCollagen
dc.subjectCollagen Type IV
dc.subjectCollagen Type XVIII
dc.subjectEndostatins
dc.subjectEndothelial Cells
dc.subjectEndothelium, Vascular
dc.subjectGene Expression Regulation, Enzymologic
dc.subjectGenes, p53
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Nude
dc.subjectNeoplasm Transplantation
dc.subjectNeoplasms, Experimental
dc.subjectNeovascularization, Pathologic
dc.subjectNeovascularization, Physiologic
dc.subjectPeptide Fragments
dc.subjectProcollagen-Proline Dioxygenase
dc.subjectTranscription, Genetic
dc.subjectTransplantation, Heterologous
dc.subjectTumor Suppressor Protein p53
dc.subjectUp-Regulation
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titlep53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase
dc.typeJournal Article
dc.source.journaltitleScience (New York, N.Y.)
dc.source.volume313
dc.source.issue5789
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1631
dc.identifier.contextkey805452
html.description.abstract<p>Recent evidence suggests that antiangiogenic therapy is sensitive to p53 status in tumors, implicating a role for p53 in the regulation of angiogenesis. Here we show that p53 transcriptionally activates the alpha(II) collagen prolyl-4-hydroxylase [alpha(II)PH] gene, resulting in the extracellular release of antiangiogenic fragments of collagen type 4 and 18. Conditioned media from cells ectopically expressing either p53 or alpha(II)PH selectively inhibited growth of primary human endothelial cells. When expressed intracellularly or exogenously delivered, alpha(II)PH significantly inhibited tumor growth in mice. Our results reveal a genetic and biochemical linkage between the p53 tumor suppressor pathway and the synthesis of antiangiogenic collagen fragments.</p>
dc.identifier.submissionpathoapubs/1631
dc.contributor.departmentProgram in Gene Function and Expression
dc.contributor.departmentHoward Hughes Medical Institute, Program in Molecular Medicine
dc.source.pages968-71


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