Implication of the ERK Pathway on the Post-transcriptional Regulation of VEGF mRNA Stability
Implication of the ERK Pathway on the Post-transcriptional Regulation of VEGF mRNA Stability
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DOI：
10.1007/978-1-60761-795-2_28
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发表时间：
2010-01-01
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影响因子：
--
通讯作者：
Pages, Gilles
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文献类型：
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作者：
Essafi-Benkhadir, Khadija;Pouyssegur, Jacques;Pages, Gilles
血管内皮生长因子- a （VEGF-A）是生理和病理血管生成的重要调控因子之一。ERK通路的组成性激活和VEGF-A的过度表达是不同来源肿瘤的共同特征。了解VEGF-A的调控对于更好地理解病理性血管生成至关重要。VEGF- a的表达在其合成的所有步骤都受到调控，包括转录、mRNA稳定性、一种被低估的VEGF调控和翻译方式。在本章中，我们通过其3'-非翻译区（3'-UTR）中富含au的序列展示了VEGF m RNA稳定性与ERK途径之间的联系。我们提出了几种方法来证明ERKs增加VEGF mRNA的半衰期。这种mRNA稳定作用部分是由于tristetrprolin （TTP）的mRNA不稳定作用的减少，TTP是一种与VEGF-A mRNA 3'-UTR结合的富含au的结合蛋白。
Vascular Endothelial Growth Factor-A (VEGF-A) is one of the most important regulators of physiological and pathological angiogenesis. Constitutive activation of the ERK pathway and over-expression of VEGF-A are common denominators of tumours of different origins. Understanding VEGF-A regulation is of primary importance to better comprehend pathological angiogenesis. VEGF-A expression is regulated at all steps of its synthesis including transcription, mRNA stability, an under estimated way of VEGF regulation and translation. In this chapter, we present the link between VEGF m RNA stability through AU-rich sequences present in its 3'-untranslated region (3'-UTR) and the ERK pathway. We present several methods that have been used to demonstrate that ERKs increase VEGF mRNA half-life. This mRNA-stabilising effect is partly due to reduction of the mRNA destabilising effects of Tristetraprolin (TTP), an AU-Rich binding protein which binds to VEGF-A mRNA 3'-UTR.