RasV12 blocks DNA synthesis and DNA damage response
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE127228 | GEO | 2019/07/02
REPOSITORIES: GEO
Similar Datasets
Project description:RasV12 blocks DNA synthesis and DNA damage response
| PRJNA524372 | ENA
Project description:We engineered KSR1-/- mouse embryonic fibroblasts (MEFs) to express GFP alone, KSR1 or RasV12 and GFP, or KSR1, H-RasV12 and GFP, and performed gene expression profiling on all 4 cell lines.
2011-04-02 | GSE28228 | GEO
Project description:C/EBPb is an auto-repressed protein that becomes posttranslationally activated by Ras-MEK-ERK signalling. C/EBPb is required for oncogene-induced senescence (OIS) of primary fibroblasts, but also displays pro-oncogenic functions in many tumour cells. Here, we show that C/EBPb activation by H-RasV12 is suppressed in immortalized/transformed cells, but not in primary cells, by its 30 untranslated region (30UTR). 30UTR sequences inhibited Ras-induced cytostatic activity of C/EBPb, DNA binding, transactivation, phosphorylation, and homodimerization, without significantly affecting protein expression. The 30UTR suppressed induction of senescence-associated C/EBPb target genes, while promoting expression of genes linked to cancers and TGFb signalling. An AU-rich element (ARE) and its cognate RNA-binding protein, HuR, were required for 30UTR inhibition. These components also excluded the Cebpb mRNA from a perinuclear cytoplasmic region that contains activated ERK1/2, indicating that the site of C/EBPb translation controls de-repression by Ras signalling. Notably, 30UTR inhibition and Cebpb mRNA compartmentalization were absent in primary fibroblasts, allowing Ras-induced C/EBPb activation and OIS to proceed. Our findings reveal a novel mechanism whereby non-coding mRNA sequences selectively regulate C/EBPb activity and suppress its anti-oncogenic functions.
2011-07-23 | GSE30834 | GEO
Project description:Targetted metabolomics in U2OS PRDX1 WT and PRDX1-/- While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential when cells are exposed to DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Subsequent analysis identified Peroxiredoxin 1, PRDX1, as fundamental for DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it is required to reduce DNA damage-induced nuclear reactive oxygen species levels. Moreover, PRDX1 controls aspartate availability, which is required for the DNA damage repair-induced upregulation of de novo nucleotide synthesis. Loss of PRDX1 leads to an impairment in the clearance of γΗ2ΑΧ nuclear foci, accumulation of replicative stress and cell proliferation defects, thus revealing a crucial role for PRDX1 as a DNA damage surveillance factor.
2022-07-19 | ST002234 | MetabolomicsWorkbench
Project description:We engineered KSR1-/- mouse embryonic fibroblasts (MEFs) to express GFP alone, KSR1 or RasV12 and GFP, or KSR1, H-RasV12 and GFP, and performed gene expression profiling on all 4 cell lines. Each cell line was measured in triplicate: 1. GFP alone 2. H-RasV12 and GFP 3. KSR1 and GFP 4. KSR1, H-RasV12, and GFP
2011-04-02 | E-GEOD-28228 | biostudies-arrayexpress
Project description:C/EBPb is an auto-repressed protein that becomes posttranslationally activated by Ras-MEK-ERK signalling. C/EBPb is required for oncogene-induced senescence (OIS) of primary fibroblasts, but also displays pro-oncogenic functions in many tumour cells. Here, we show that C/EBPb activation by H-RasV12 is suppressed in immortalized/transformed cells, but not in primary cells, by its 30 untranslated region (30UTR). 30UTR sequences inhibited Ras-induced cytostatic activity of C/EBPb, DNA binding, transactivation, phosphorylation, and homodimerization, without significantly affecting protein expression. The 30UTR suppressed induction of senescence-associated C/EBPb target genes, while promoting expression of genes linked to cancers and TGFb signalling. An AU-rich element (ARE) and its cognate RNA-binding protein, HuR, were required for 30UTR inhibition. These components also excluded the Cebpb mRNA from a perinuclear cytoplasmic region that contains activated ERK1/2, indicating that the site of C/EBPb translation controls de-repression by Ras signalling. Notably, 30UTR inhibition and Cebpb mRNA compartmentalization were absent in primary fibroblasts, allowing Ras-induced C/EBPb activation and OIS to proceed. Our findings reveal a novel mechanism whereby non-coding mRNA sequences selectively regulate C/EBPb activity and suppress its anti-oncogenic functions. NIH-3T3 cells were retrovirally infected and selected with appropriate antiobiotics. Equal number of cells were plated and collected 48-72 hours later.
2011-07-22 | E-GEOD-30834 | biostudies-arrayexpress
Project description:The goal of this study is to profile gene expression patterns of RasV12-induced brain tumors and tumor-associated macrophages (TAM) in the cerebellum. Ras activation in Msi1+ cells induced tumor formation in the cerebellum of Msi1-CreER;RasV12 mice (Ras). GFP+ tumor cells and CD11b+ phagocytes were isolated from the cerebellum of Ras mice at 3 weeks and used for gene expression analysis. GFP+ cells and CD11b+ phagocytes isolated from the cerebellum of Msi1-CreER;GFP mice (Cont) were used as control.
2021-03-31 | GSE128012 | GEO
Project description:Newly emerging transformed cells carrying genetic defects, including the active Ras mutant, are apicall extruded when surrounded by normal epithelial cells. This biological phenomenon is termed as cell competition. It remains elusive which factors prime RasV12-transformed cells to be expelled via cell competition. Here, We performe microarray analysis to search for molecules whose expression is changed in RasV12 cells surrounded by normal cells.
2023-07-11 | GSE236658 | GEO
Project description:Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into apical lumen via cell competition. However, it remains elusive which internal or external factors compromise cell competition and provoke oncogenesis. Here, we examine the effect of sequential accumulation of gene mutations mimicking multi-sequential carcinogenesis on RasV12-induced cell competition. Consequently, we find that directionality of cell extrusion of RasV12 cells mosaically produced within Wnt-activated epithelia is reversed, and transformed cells are delaminated into basal lamina via non-cell autonomous MMP21 upregulation. Elevated production of MMP21 is elicited partly through NF-κB signaling, which blockage restores apical elimination of RasV12 cells. Collectively, this study demonstrates that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells and are endowed with an invasion advantage. We performed microarray analysis to search for molecules whose expression is changed in β-catenin Δ131/RasV12 cells surrounded by β-catenin Δ131 cells.
2022-11-16 | GSE217830 | GEO
Project description:To investigate which factors might be driving the cachectic muscle wasting observed in our larval models bearing RasV12, scrib1 tumors, we performed RNA sequencing (RNAseq) on the cuticles of wild type and RasV12, scrib1 tumour-bearing larvae. Pathway and gene ontology analysis revealed significant deregulation of stress and starvation response genes, metabolic genes, and inflammation and immune regulatory genes within cachectic muscle of tumour bearing larvae.
2021-06-17 | GSE178332 | GEO