Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA124089 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recurrent Glycogen synthase kinase-3 (GSK-3) phosphorylates multiple splicing factors, including SRSF2, and regulates the splicing of a broad range of mRNAs in human cells. Inhibition of GSK-3 disrupts splicing and promotes cell death in hematopoietic cells with heterozygous mutations in SRSF2 and not in cells with wild-type splicing factors. To characterize how GSK-3 inhibition alters the cellular proteome in SRSF2-P95H/+ cells, we have performed quantitative mass spectrometry (qMS) on K562 cells with SRSF2P95H/+ knocked into the endogenous locus (PMID 30799057) and parental K562 cells, treated with the GSK-3 inhibitor CHIR99021. We focused on the mitochondrial proteome using human proteome (UniprotKB) and mitochondrial (MitoCarta 3.0) databases for protein identification, identifying 163 mitochondrial proteins whose levels are affected by SRSF2 mutation.
2024-06-22 | PXD043213 | Pride
Project description:The Glycogen Synthase Kinase-3 Phosphoproteome: GSK-3 Phosphorylates Multiple Splicing Factors and Regulates Alternative Splicing
| PRJNA356332 | ENA
Project description:Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. Over 100 putative GSK-3 substrates have been reported in diverse cell types based on in vitro kinase assays or genetic and pharmacological manipulation of GSK-3. Many more have been predicted based on a recurrent GSK-3 consensus motif, but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. We used stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry to analyze the repertoire of GSK-3 dependent substrates in mouse embryonic stem cells (ESCs). A comparison of wild-type and Gsk3a;Gsk3b knockout (DKO) ESCs revealed prominent GSK-3-dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis, as well as proteins that regulate transcription, translation, and cell division. We demonstrate direct, GSK-3-dependent phosphorylation of the splicing factors RBM8A and PSF as well as the nucleolar protein NPM1. RNA sequencing to compare the transcriptomes of wild-type and Gsk3 DKO ESCs identified more than 210 genes that are alternatively spliced in a GSK-3-dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. Overall, this study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence for GSK-3 as a regulator of alternative splicing.
2017-08-24 | GSE90921 | GEO
Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2. Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome. Keywords: Gene expression array-based The study was designed to examine the changes in gene expression between wild-type and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.
2010-11-15 | E-GEOD-20015 | biostudies-arrayexpress
Project description:Glycogen synthase kinase-3β (GSK-3β) has been recently identified as an important regulator of stem cell function. In vitro studies show that GSK-3β inhibition delays proliferation of human haematopoietic progenitor cells while increasing numbers of late dividing multipotent progenitors. Gene expression analysis revealed that GSK-3β inhibition modulates the expression of a subset of genes that are transcriptional targets for cytokines. GSK-3β inhibition antagonised down-regulation of genes encoding cyclin dependent kinase inhibitor p57 and a member of the growth arrest and DNA damage 45 family, GADD45B as well as up-regulation of cyclin D1 by cytokines, providing a possible mechanism for the BIO-induced delay in cell cycle progression. Surprisingly, inhibition of GSK-3β earlier shown to prevent β-catenin degradation and promote the nuclear accumulation of β-catenin was not sufficient to activate its transcriptional targets in haematopoietic stem cells. GSK-3β inhibition up-regulated the expression of a several positive regulators of stem cell function suppressed during cytokine-induced proliferation. The data supports a clinical role for GSK-3β inhibition to improve engraftment efficiency of ex vivo expanded stem cells. Total RNA was isolated from three groups following expansion of CD34+ cells in cytokikes and then treatment with BIO, as described below.
2010-04-07 | E-GEOD-21073 | biostudies-arrayexpress
Project description:Tissue-specific regulation of gene expression is essential for multicellular organisms, and RNA binding proteins play central roles in these molecular processes. To determine how the Caenorhabditis elegans RNA binding protein ADR-1 regulates tissue-specific gene expression, we profiled the binding targets of ADR-1 in neural cells and assessed the effects of ADR-1 RNA binding on neural gene expression. We identified a cohort of neural transcripts that facilitate lipid synthesis and are directly regulated by ADR-1 RNA binding. To identify cellular factors that influence ADR-1 binding, a forward genetic screen was performed, revealing that the serine/threonine protein kinase, glycogen synthase kinase-3 (GSK-3), inhibits ADR-1 binding to the cohort. Further investigation revealed that RNA binding protein VIG-1, promotes ADR-1 binding to the cohort in a GSK-3-dependent manner. Together, we reveal that interplay between kinases and RNA binding proteins regulates expression of lipid metabolism genes within neural cells, potentially impacting stress resistance and longevity.
2025-03-07 | GSE286247 | GEO
Project description:Tissue-specific regulation of gene expression is essential for multicellular organisms, and RNA binding proteins play central roles in these molecular processes. To determine how the Caenorhabditis elegans RNA binding protein ADR-1 regulates tissue-specific gene expression, we profiled the binding targets of ADR-1 in neural cells and assessed the effects of ADR-1 RNA binding on neural gene expression. We identified a cohort of neural transcripts that facilitate lipid synthesis and are directly regulated by ADR-1 RNA binding. To identify cellular factors that influence ADR-1 binding, a forward genetic screen was performed, revealing that the serine/threonine protein kinase, glycogen synthase kinase-3 (GSK-3), inhibits ADR-1 binding to the cohort. Further investigation revealed that RNA binding protein VIG-1, promotes ADR-1 binding to the cohort in a GSK-3-dependent manner. Together, we reveal that interplay between kinases and RNA binding proteins regulates expression of lipid metabolism genes within neural cells, potentially impacting stress resistance and longevity.
2025-03-07 | GSE286246 | GEO
Project description:The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2. Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome. Keywords: Gene expression array-based
2010-11-15 | GSE20015 | GEO
Project description:Tissue-specific regulation of gene expression is essential for multicellular organisms, and RNA binding proteins play central roles in these molecular processes. To determine how the Caenorhabditis elegans RNA binding protein ADR-1 regulates tissue-specific gene expression, we profiled the binding targets of ADR-1 in neural cells and assessed the effects of ADR-1 RNA binding on neural gene expression. We identified a cohort of neural transcripts that facilitate lipid synthesis and are directly regulated by ADR-1 RNA binding. To identify cellular factors that influence ADR-1 binding, a forward genetic screen was performed, revealing that the serine/threonine protein kinase, glycogen synthase kinase-3 (GSK-3), inhibits ADR-1 binding to the cohort. Further investigation revealed that RNA binding protein VIG-1, promotes ADR-1 binding to the cohort in a GSK-3-dependent manner. Together, we reveal that interplay between kinases and RNA binding proteins regulates expression of lipid metabolism genes within neural cells, potentially impacting stress resistance and longevity.
2025-02-21 | MSV000097188 | MassIVE
Project description:Glycogen synthase kinase-3β (GSK-3β) has been recently identified as an important regulator of stem cell function. In vitro studies show that GSK-3β inhibition delays proliferation of human haematopoietic progenitor cells while increasing numbers of late dividing multipotent progenitors. Gene expression analysis revealed that GSK-3β inhibition modulates the expression of a subset of genes that are transcriptional targets for cytokines. GSK-3β inhibition antagonised down-regulation of genes encoding cyclin dependent kinase inhibitor p57 and a member of the growth arrest and DNA damage 45 family, GADD45B as well as up-regulation of cyclin D1 by cytokines, providing a possible mechanism for the BIO-induced delay in cell cycle progression. Surprisingly, inhibition of GSK-3β earlier shown to prevent β-catenin degradation and promote the nuclear accumulation of β-catenin was not sufficient to activate its transcriptional targets in haematopoietic stem cells. GSK-3β inhibition up-regulated the expression of a several positive regulators of stem cell function suppressed during cytokine-induced proliferation. The data supports a clinical role for GSK-3β inhibition to improve engraftment efficiency of ex vivo expanded stem cells.
2010-03-26 | GSE21073 | GEO