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p53-Mediated Inhibition of Angiogenesis Through Up-Regulation of a Collagen Prolyl Hydroxylase
Jose G. Teodoro,Albert E. Parker,Xiaochun Zhu,Michael R. Green*
Recent evidence suggests that antiangiogenic therapy is sensitiveto p53 status in tumors, implicating a role for p53 in the regulationof angiogenesis. Here we show that p53 transcriptionally activatesthe (II) collagen prolyl-4-hydroxylase [(II)PH] gene, resultingin the extracellular release of antiangiogenic fragments ofcollagen type 4 and 18. Conditioned media from cells ectopicallyexpressing either p53 or (II)PH selectively inhibited growthof primary human endothelial cells. When expressed intracellularlyor exogenously delivered, (II)PH significantly inhibited tumorgrowth in mice. Our results reveal a genetic and biochemicallinkage between the p53 tumor suppressor pathway and the synthesisof antiangiogenic collagen fragments.
Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
* To whom correspondence should be addressed. E-mail: michael.green{at}umassmed.edu
Linking Antibody Fc Domain to Endostatin Significantly Improves Endostatin Half-life and Efficacy.
T.-Y. Lee, R. M. Tjin Tham Sjin, S. Movahedi, B. Ahmed, E. A. Pravda, K.-M. Lo, S. D. Gillies, J. Folkman, and K. Javaherian (2008)
Clin. Cancer Res.
14, 1487-1493
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Succinate inhibition of {alpha}-ketoglutarate-dependent enzymes in a yeast model of paraganglioma.
E. H. Smith, R. Janknecht, and L. J. Maher III (2007)
Hum. Mol. Genet.
16, 3136-3148
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PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells.
T.-C. Ho, S.-L. Chen, Y.-C. Yang, C.-L. Liao, H.-C. Cheng, and Y.-P. Tsao (2007)
Cardiovasc Res
76, 213-223
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Y. Zhou, Y. Zhong, Y. Wang, X. Zhang, D. L. Batista, R. Gejman, P. J. Ansell, J. Zhao, C. Weng, and A. Klibanski (2007)
J. Biol. Chem.
282, 24731-24742
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Transcriptional network governing the angiogenic switch in human pancreatic cancer.
A. Abdollahi, C. Schwager, J. Kleeff, I. Esposito, S. Domhan, P. Peschke, K. Hauser, P. Hahnfeldt, L. Hlatky, J. Debus, et al. (2007)
PNAS
104, 12890-12895
|Abstract »|Full Text »|PDF »
Inhibition of p53-Murine Double Minute 2 Interaction by Nutlin-3A Stabilizes p53 and Induces Cell Cycle Arrest and Apoptosis in Hodgkin Lymphoma.
E. Drakos, A. Thomaides, L. J. Medeiros, J. Li, V. Leventaki, M. Konopleva, M. Andreeff, and G. Z. Rassidakis (2007)
Clin. Cancer Res.
13, 3380-3387
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Vascular Endothelial Growth Factor and Its Relationship to Inflammatory Mediators.
Calcitriol Is a Potent Inhibitor of Retinal Neovascularization.
D. M. Albert, E. A. Scheef, S. Wang, F. Mehraein, S. R. Darjatmoko, C. M. Sorenson, and N. Sheibani (2007)
Invest. Ophthalmol. Vis. Sci.
48, 2327-2334
|Abstract »|Full Text »|PDF »
Tumor Suppression by p53 Is Mediated in Part by the Antiangiogenic Activity of Endostatin and Tumstatin.
(II) collagen prolyl-4-hydroxylase [
