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• W2014595259 endingPage "2058" @default.
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• W2014595259 abstract "Corruption of the normal function of the cellular prion protein (PrP(C)) by the scrapie isoform (PrP(Sc)) emerges as a critical causal event in Transmissible Spongiform Encaphalopathies (TSE) pathogenesis. However, PrP(C) physiological role remains unclear. By exploiting the properties of the 1C11 neuroectodermal cell line, able to convert into 1C11(5-HT) serotonergic or 1C11(NE) noradrenergic neuronal cells, we assigned a signaling function to PrP(C). Here, we establish that antibody-mediated PrP(C) ligation promotes the recruitment of the cAMP responsive element binding protein (CREB) transcription factor downstream from the MAPK ERK1/2, in 1C11 precursor cells and their 1C11(5-HT) and 1C11(NE) neuronal progenies. Whatever the differentiation state of 1C11 cells, the PrP(C)-dependent CREB activation triggers Egr-1 and c-fos transcription, two immediate early genes that relay CREB's role in cell survival and proliferation as well as in neuronal plasticity. Furthermore, in 1C11-derived neuronal cells, we draw a link between the PrP(C)-CREB coupling and a transcriptional regulation of the metalloproteinase MMP-9 and its inhibitor TIMP-1, which play pivotal roles in neuronal pathophysiology. Finally, the PrP(C)-dependent control on MMP-9 impacts on the processing of the transmembrane protein, beta-dystroglycan. Taken together, our data define molecular mechanisms that likely mirror PrP(C) ubiquitous contribution to cytoprotection and its involvement in neuronal plasticity." @default.
• W2014595259 created "2016-06-24" @default.
• W2014595259 creator A5022031992 @default.
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• W2014595259 creator A5056729695 @default.
• W2014595259 creator A5082113937 @default.
• W2014595259 date "2008-11-01" @default.
• W2014595259 modified "2023-10-16" @default.
• W2014595259 title "CREB-dependent gene regulation by prion protein: Impact on MMP-9 and β-dystroglycan" @default.
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• W2014595259 doi "https://doi.org/10.1016/j.cellsig.2008.07.016" @default.
• W2014595259 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18718863" @default.
• W2014595259 hasPublicationYear "2008" @default.
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