en
Scientific article
English

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

Published inMolecular and cellular biology, vol. 28, no. 5, p. 1630-1643
Publication date2008
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
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. 1630–1643. doi: 10.1128/MCB.01767-07
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal0270-7306
572views
0downloads

Technical informations

Creation02/13/2009 11:34:00 AM
First validation02/13/2009 11:34:00 AM
Update time03/14/2023 3:00:31 PM
Status update03/14/2023 3:00:30 PM
Last indexation01/15/2024 6:11:07 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack