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Title

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
Authors
Fujita, Toshitsugu
Ryser, Stephan
Piuz, Isabelle
Schlegel, Werner
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 Animals — Cell Culture Techniques — Cells Cultured — Chromatin Immunoprecipitation — Culture Media Serum-Free — Cyclin-Dependent Kinase 9/metabolism — Extracellular Signal-Regulated MAP Kinases/metabolism — Genes Immediate-Early — Models Biological — Phosphorylation/drug effects — Pituitary Gland/cytology — Positive Transcriptional Elongation Factor B/metabolism — Precipitin Tests — Rats — Signal Transduction — Thyrotropin-Releasing Hormone/pharmacology — Time Factors — Transcription Genetic — Up-Regulation
Identifiers
PMID: 18086894
Full text
Article (Accepted version) (871 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://mcb.asm.org/cgi/content/full/28/5/1630?view=long&pmid=18086894
Structures
Faculté de médecine / Section de médecine clinique / Département de médecine
Citation
(ISO format) 		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. doi: 10.1128/MCB.01767-07 https://archive-ouverte.unige.ch/unige:794

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Deposited on : 2009-02-13

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