Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis
| Autor: | Nathalie M. Mazure, Jacques Pouysségur, M. C. Brahimi-Horn |
|---|---|
| Přispěvatelé: | Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis MESH: Cell Hypoxia Gene Expression Endothelial Growth Factors MESH: Vascular Endothelial Growth Factors Neovascularization chemistry.chemical_compound 0302 clinical medicine MESH: Endothelial Growth Factors Drug Discovery Nuclear protein Lymphokines 0303 health sciences Neovascularization Pathologic Vascular Endothelial Growth Factors Kinase Nuclear Proteins MESH: Transcription Factors Cell Hypoxia 3. Good health Cell biology DNA-Binding Proteins Vascular endothelial growth factor Vascular endothelial growth factor A 030220 oncology & carcinogenesis Intercellular Signaling Peptides and Proteins Hypoxia-Inducible Factor 1 Mitogen-Activated Protein Kinases medicine.symptom MESH: Neovascularization Physiologic Transcriptional Activation MESH: Gene Expression Neovascularization Physiologic [SDV.CAN]Life Sciences [q-bio]/Cancer Biology MESH: Endothelium MESH: Hypoxia-Inducible Factor 1 alpha Subunit 03 medical and health sciences medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Endothelium MESH: Intercellular Signaling Peptides and Proteins Transcription factor 030304 developmental biology Pharmacology MESH: Humans MESH: Lymphokines MESH: Vascular Endothelial Growth Factor A Hypoxia-Inducible Factor 1 alpha Subunit MESH: Mitogen-Activated Protein Kinases HIF1A MESH: Hypoxia-Inducible Factor 1 chemistry MESH: Trans-Activation (Genetics) MESH: Neovascularization Pathologic MESH: Nuclear Proteins MESH: DNA-Binding Proteins Transcription Factors |
| Zdroj: | Current Pharmaceutical Design Current Pharmaceutical Design, Bentham Science Publishers, 2003, 9 (7), pp.531-41 |
| ISSN: | 1381-6128 |
| Popis: | International audience; In the last few decades it has become clear that detailed understanding of the mechanisms of angiogenesis, a process leading to growth of new blood vessels, should lead to improved treatment of diseases such as ischemic disorders and cancer where neovascularization is impaired or activated, respectively. In this review, we will outline some of our recent findings concerning the regulation of the vascular endothelial growth factor (VEGF), a key player in angiogenesis and one of its transcription factors, the hypoxia-inducible factor-1 (HIF-1) a master gene product driving adaptation to hypoxia. We will discuss the observation that growth factors and oncogenic transformation via the mitogen-activated protein kinases p42/p44 MAPKs not only activate the VEGF promoter through the Sp1/AP-2 transcriptional factor complex but also phosphorylate HIF-1alpha leading in turn to enhance HIF-1 dependent transcriptional activation of VEGF. The stress-activated protein kinases (SAPK) also contribute to angiogenesis by stabilizing VEGF mRNA. Finally, we will present recent advances into oxygen-sensing, in particular the HIF-hydroxylases that govern HIF-1alpha instability (PHD2) or inactivation (FIH-1). The revelation of these oxygen sensors has provided pharmacologists with new molecular targets for the development of novel therapies to control angiogenesis either positively or negatively. |
| Databáze: | OpenAIRE |
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