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Up-regulation of P-TEFb by the MEK1-extracellular signal-regulated kinase signaling pathway contributes to stimulated transcription elongation of immediate early genes in neuroendocrine cells

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Published in Molecular and Cellular Biology. 2008, vol. 28, no. 5, p. 1630-43
Abstract The positive elongation factor P-TEFb appears to function as a crucial C-terminal-domain (CTD) kinase for RNA polymerase II (Pol II) transcribing immediate early genes (IEGs) in neuroendocrine GH4C1 cells. Chromatin immunoprecipitation indicated that in resting cells Pol II occupied the promoter-proximal regions of the c-fos and junB genes, together with the negative elongation factors DSIF and NELF. Thyrotropin-releasing hormone (TRH)-induced recruitment of positive transcription elongation factor b (P-TEFb) abolished the pausing of Pol II and enhanced phosphorylation of CTD serine 2, resulting in transcription elongation. In addition, P-TEFb was essential for splicing and 3'-end processing of IEG transcripts. Importantly, the MEK1-extracellular signal-regulated kinase (ERK) signaling pathway activated by TRH up-regulated nuclear CDK9 and CDK9/cyclinT1 dimers (i.e., P-TEFb), facilitating the recruitment of P-TEFb to c-fos and other IEGs. Thus, in addition to established gene transcription control via promoter response elements, the MEK1-ERK signaling pathway controls transcription elongation by Pol II via the up-regulation of nuclear CDK9 integrated into P-TEFb.
Keywords AnimalsCell Culture TechniquesCells CulturedChromatin ImmunoprecipitationCulture Media Serum-FreeCyclin-Dependent Kinase 9/metabolismExtracellular Signal-Regulated MAP Kinases/metabolismGenes Immediate-EarlyModels BiologicalPhosphorylation/drug effectsPituitary Gland/cytologyPositive Transcriptional Elongation Factor B/metabolismPrecipitin TestsRatsSignal TransductionThyrotropin-Releasing Hormone/pharmacologyTime FactorsTranscription GeneticUp-Regulation
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PMID: 18086894
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FUJITA, Toshitsugu et al. Up-regulation of P-TEFb by the MEK1-extracellular signal-regulated kinase signaling pathway contributes to stimulated transcription elongation of immediate early genes in neuroendocrine cells. In: Molecular and Cellular Biology, 2008, vol. 28, n° 5, p. 1630-43. https://archive-ouverte.unige.ch/unige:794

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Deposited on : 2009-02-13

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