Implication of the ERK pathway on the post-transcriptional regulation of VEGF mRNA stability.
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 mRNA 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.
Essafi-Benkhadir
Khadija
K
Biochemistry and Experimental Pathology Unit, Pasteur Institute of Tunis, Tunis, Tunisia.
Pouysségur
Jacques
J
Pagès
Gilles
G
D020413:3' Untranslated Regions / Q000235:genetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003513:Cycloheximide / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000378:metabolism; D051816:Tristetraprolin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D020413:3' Untranslated Regions; C110962:5,6-dichlorobenzimidazole; D001562:Benzimidazoles; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D051816:Tristetraprolin; D042461:Vascular Endothelial Growth Factor A; D003513:Cycloheximide; D008156:Luciferases; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase