Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression
Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression
Signaling by transforming growth factor (TGF)-beta family members is mediated by Smad proteins that regulate gene transcription through functional cooperativity and association with other DNA-binding proteins. The hypoxia-inducible factor (HIF)-1 is a transcriptional complex that plays a key role in oxygen-regulated gene expression. We demonstrate that hypoxia and TGF-beta cooperate in the induction of the promoter activity of vascular endothelial growth factor (VEGF), which is a major stimulus in the promotion of angiogenesis. This cooperation has been mapped on the human VEGF promoter within a region at -1006 to -954 that contains functional DNA-binding sequences for HIF-1 and Smads. Optimal HIF-1alpha-dependent induction of the VEGF promoter was obtained in the presence of Smad3, suggesting an interaction between these proteins. Consistent with this, co-immunoprecipitation experiments revealed that HIF-1alpha physically associates with Smad3. These results demonstrate that both TGF-beta and hypoxia signaling pathways can synergize in the regulation of VEGF gene expression at the transcriptional level.
38527-38535
Sánchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Botella, Luisa M.
33922361-7216-4770-8b71-fc2369e7df06
Velasco, Beatriz
c8fc68a3-8b68-4306-adcc-979b4243fa0c
Corbí, Angel
add9a055-4414-4e08-8cf1-9f3054b8fc9c
Attisano, Liliana
309e1c46-6f2e-49f5-92eb-9c70ca4938c0
Bernabéu, Carmelo
30da3b6d-c832-4d23-8ea8-79e4c808ca05
19 October 2001
Sánchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Botella, Luisa M.
33922361-7216-4770-8b71-fc2369e7df06
Velasco, Beatriz
c8fc68a3-8b68-4306-adcc-979b4243fa0c
Corbí, Angel
add9a055-4414-4e08-8cf1-9f3054b8fc9c
Attisano, Liliana
309e1c46-6f2e-49f5-92eb-9c70ca4938c0
Bernabéu, Carmelo
30da3b6d-c832-4d23-8ea8-79e4c808ca05
Sánchez-Elsner, Tilman, Botella, Luisa M., Velasco, Beatriz, Corbí, Angel, Attisano, Liliana and Bernabéu, Carmelo
(2001)
Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression.
The Journal of Biological Chemistry, 276 (42), .
(doi:10.1074/jbc.M104536200).
Abstract
Signaling by transforming growth factor (TGF)-beta family members is mediated by Smad proteins that regulate gene transcription through functional cooperativity and association with other DNA-binding proteins. The hypoxia-inducible factor (HIF)-1 is a transcriptional complex that plays a key role in oxygen-regulated gene expression. We demonstrate that hypoxia and TGF-beta cooperate in the induction of the promoter activity of vascular endothelial growth factor (VEGF), which is a major stimulus in the promotion of angiogenesis. This cooperation has been mapped on the human VEGF promoter within a region at -1006 to -954 that contains functional DNA-binding sequences for HIF-1 and Smads. Optimal HIF-1alpha-dependent induction of the VEGF promoter was obtained in the presence of Smad3, suggesting an interaction between these proteins. Consistent with this, co-immunoprecipitation experiments revealed that HIF-1alpha physically associates with Smad3. These results demonstrate that both TGF-beta and hypoxia signaling pathways can synergize in the regulation of VEGF gene expression at the transcriptional level.
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Published date: 19 October 2001
Additional Information:
This work was supported in part by Grants SAF2000-0132 and SAF98/0068 from the Ministerio de Ciencia y Tecnología and Comunidad Autónoma de Madrid.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Identifiers
Local EPrints ID: 47978
URI: http://eprints.soton.ac.uk/id/eprint/47978
ISSN: 0021-9258
PURE UUID: 0444565f-eb08-4617-ace2-35a6ac1c3fac
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Date deposited: 16 Aug 2007
Last modified: 16 Mar 2024 03:56
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Contributors
Author:
Luisa M. Botella
Author:
Beatriz Velasco
Author:
Angel Corbí
Author:
Liliana Attisano
Author:
Carmelo Bernabéu
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