Proteosome-Erk dependent transcriptional events
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE110877 | GEO | 2019/08/08
REPOSITORIES: GEO
Similar Datasets
Project description:Proteosome-Erk dependent transcriptional events
| PRJNA434732 | ENA
Project description:Transcriptome analysis of ESCs treated with a transcription inhibitor, with our without ERK activity to measure Erk-dependent changes in mRNA degradation
2019-08-08 | GSE110664 | GEO
Project description:RNA-seq were performed with six samples, WT KH2 ESCs treated with or without PD0325901 for 48 hours (KH2_PD and KH2, respectively), iErk1; Erk KO ESCs cultured in the presence Dox (P0), 48 and 96 hours after Dox withdrawal (P1 and P2, respectively), and iErk1; Erk KO ESCs cultured without Dox for 96 hours, and treated with PD0325901 in the last 48 hours (P2_PD). iErk1; Erk KO ESCs cultured without Dox does not express Erk, thus mimicking Erk KO.
2015-09-29 | GSE70304 | GEO
Project description:Transcriptome analysis of ESCs harboring an 4OHT-inducible cRAF for 0h, 8h, 10h, or 8h followed by a 2h inhibition with a chemical inhibitor
2019-08-08 | GSE110662 | GEO
Project description:Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification we explore the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function experiments reveal a role for Erk signaling in suppressing endodermal differentiation, but not neural specification. Activation of Erk signaling in ESCs de-represses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming while sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation. We use microarray analysis to determine the transcription response to Erk1/2 in mouse embryonic stem cells across a 24 hour window of time Mouse ESCs carrying a tamoxifen inducible constitutively active c-Raf fusion protein were stimulated for 6 time points (30minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours) in the presence of 250nM PD173074. Uninduced (0h hours) and DMSO only treated cells served as controls.
2015-01-01 | E-GEOD-59755 | biostudies-arrayexpress
Project description:Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification we explore the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function experiments reveal a role for Erk signaling in suppressing endodermal differentiation, but not neural specification. Activation of Erk signaling in ESCs de-represses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming while sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation. We use microarray analysis to determine the transcription response to Erk1/2 in mouse embryonic stem cells across a 24 hour window of time
2015-01-01 | GSE59755 | GEO
Project description:The series of events that allows for the conversion of adherent epithelial cells into migratory cells is collectively known as epithelial-mesenchymal transition (EMT). EMT is involved in triggering neural crest migration during development and in the pathogenesis of diseases, such as cancer metastasis. Whereas Erk signalling is known to be essential for EMT, its influence on the epigenetic and transcriptional programme underlying EMT is poorly understood. Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene expression in primary mammary epithelial cells undergoing EMT, we found that Erk signalling is essential for the epigenetic reprogramming underlying hallmark gene expression and phenotypic changes of EMT. We found that the chemical inhibition of Erk signalling during EMT prevents loss and gain of H3K27ac mark at regulatory regions of epithelial and mesenchymal genes, respectively, and results in a transcriptome and epigenome closer to those of epithelial cells. Further computational analyses identified a distinct set of transcription factor motifs enriched at distal regulatory regions that are epigenetically remodelled by Erk signalling. Altogether, our study reveal an Erk-dependent epigenetic remodelling of distal regulatory elements that results in a gene expression programme that is essential for driving EMT.
2017-06-13 | GSE92333 | GEO
Project description:Mutational activation of the KRAS oncogene is a major genetic driver of pancreatic ductal adenocarcinoma (PDAC) growth. KRAS-dependent PDAC growth is mediated primarily through persistent activation of the RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cascade, one of the most extensively studied cancer signaling networks. While substrates of RAF and MEK kinases are highly restricted, ERK1/2 has been attributed to over 1,000 substrates. In this study, we used the highly selective ERK1/2 inhibitor, SCH772984, and proteomic and phosphoproteomic analyses to extend the repertoire of ERK-dependent phosphosites and phosphoproteins in PDAC. We validated the specificity of SCH772984 in our cell lines using multiplexed inhibitor beads coupled with mass spectrometry (MIB/MS). We then performed phosphoproteomics and global proteomics in a panel of PDAC cell lines and identified 5,117 ERK-dependent phosphosites on 2,252 proteins, of which 88% and 67%, respectively, were not previously associated with ERK. We then utilized our recently annotated serine/threonine kinome motif database to dissect the phosphoproteome and reveal an expansive ERK-regulated kinase network. We found that ERK- and immediate downstream kinase RSK-substrate motifs predominated after one hour of ERK inhibition, whereas cell cycle regulatory cyclin-dependent kinase motifs predominated by 24 h, reflecting a highly dynamic ERK-dependent phosphoproteome. We find compensatory activation of HIPK, CLK, PKN, PAK, and DYRK family kinases. Finally, using the genome-wide CRISPR-Cas9 dataset in the Cancer Dependency Map portal (DepMap), we determined that approximately 18% of ERK dependent phosphoproteins are essential for pancreatic cancer growth, and these are enriched in nuclear proteins. Together, our findings provide a system-wide profile of the mechanistic basis for ERK-driven pancreatic cancer growth.
2024-05-29 | PXD048532 | Pride
Project description:Studies were undertaken to determine whether oscillatory behavior in the extracellular signal regulated kinase (ERK) pathway results in unique gene regulation patterns. Microarray analysis was performed on three subcloned populations of human keratinocytes with distinct ERK signaling/oscillation phenotypes. Microarray analysis identified 45 genes that overlapped between 2 subclones with oscillation phenotypes but not in the subclone which is non-oscillatory. Transcription factor networks revealed a role for MED1 in mediating ERK oscillation-dependent gene expression, which was confirmed with Western blot analysis. Further experimentation confirmed a role for p38 in the mediation of MED1 phosphorylation and ERK oscillatory behavior. hTERT-immortalized normal human keratinocytes (provided by Dr. Jerry Shay, The University of Texas Southwestern Medical Center) were stably transfected with ERK1-green fluorescent protein chimera and stable subclones were isolated with distinct ERK activation/oscillation patterns: Clone #1 exhibits transient ERK activation with ligand activation but does not oscillate; Clone #2 exhibits persistent ERK oscillations that are dependent on ligand activation; and Clone #3 exhibits spontaneous ERK oscillations in the absence of ligand activation.
2014-03-13 | E-GEOD-55823 | biostudies-arrayexpress