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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Goukassian, David A. Dolan, Christine M. Curry, Cynthia Murayama, Toshinori Dinesh, Deepika Qin, Gangjian Kearney, Marianne Thorne, Tina Hanley, Allison Losordo, Douglas W. Silver, Marcy Kishore, Raj Luedemann, Corinne N. Heyd, Lindsay Martelli, Fabio Wecker, Andrea Zhu, Yan |
| Description | Author Affiliation: Qin G ( Division of Cardiovascular Research, Tufts University School of Medicine, Caritas St. Elizabeth's Medical Center, Boston, MA 02135, USA. gangjian.qin@tuffs.edu); |
| Abstract | The transcription factor E2F1 is known to regulate cell proliferation and has been thought to modulate tumorigenesis via this mechanism alone. Here we show that mice deficient in E2F1 exhibit enhanced angiogenesis. The proangiogenic phenotype in E2F1 deficiency is the result of overproduction of vascular endothelial growth factor (VEGF) and is prevented by VEGF blockade. Under hypoxic conditions, E2F1 down-regulates the expression of VEGF promoter activity by associating with p53 and specifically down-regulating expression of VEGF but not other hypoxia-inducible genes, suggesting a promoter structure context-dependent regulation mechanism. We found that the minimum VEGF promoter mediating transcriptional repression by E2F1 features an E2F1- binding site with four Sp-1 sites in close proximity. These data disclose an unexpected function of endogenous E2F1: regulation of angiogenic activity via p53-dependent transcriptional control of VEGF expression. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 29 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle E2F1 Transcription Factor Metabolism Transcription, Genetic Genetics Tumor Suppressor Protein P53 Vascular Endothelial Growth Factor A Biosynthesis Animals Cells, Cultured Down-Regulation Deficiency Hindlimb Blood Supply Mice Mice, Inbred C57BL Mice, Knockout Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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