The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.
wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
We have investigated the effects of flavopiridol, a novel protein kinase inhibitor that is selective for cyclin-dependent kinases, on hypoxia-induced vascular endothelial growth factor (VEGF) expression in human monocytes. We found that hypoxia induces a time-dependent increase of VEGF mRNA expression and protein levels in human monocytes. Flavopiridol showed a minimal effect on the constitutive levels of VEGF mRNA but completely blocked hypoxia-induced VEGF mRNA and protein expression. The inhibitory effects of flavopiridol on VEGF mRNA induction also occurred in the presence of cycloheximide. The transcriptional activation of either a VEGF promoter-luciferase construct or a hypoxia-inducible factor 1 reporter plasmid was not affected by addition of flavopiridol in transient transfection experiments. In contrast, actinomycin D experiments demonstrated that flavopiridol dramatically decreased VEGFmRNA stability. These data provide the first evidence that flavopiridol can affect gene expression by altering mRNA stability. We propose that flavopiridol may interfere with one or more signaling events, leading to hypoxia-induced, protein kinase-modulated, RNA protein binding activity. An important clinical implication of our results is that flavopiridol, presently under investigation in clinical trials, might have antiangiogenic as well as direct antiproliferative effects.[1]
