Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA90293 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Apoptotic neuron death is a common feature of many neurodegenerative diseases. Perhaps surprisingly, the exact mechanisms by which neurons undergo apoptosis have yet to be elucidated. We conducted an unbiased whole genome screen in human neurons to discover genes required for apoptotic neuron death, and found ATF2, MAP3K12 and JUN among top hits. We demonstrate that ATF2 is a previously unappreciated master regulator of neuron death. ATF2 is phosphorylated downstream of MAP3K12 (dual leucine zipper kinase) and MAP3K13 (leucine zipper kinase) and its phosphorylation is essential for transcriptional upregulation of JUN. We show that JUN upregulation is essential for apoptosis – but not its phosphorylation. Contrary to previous assumptions, cJun phosphorylation is therefore simply a correlate of JUN upregulation. In this study, we identify phosphorylation of ATF2 as a key event in the mechanism of neuronal apoptosis, linking the MAP3K12/13 kinase cascade to transcriptional upregulation of JUN. Since targeting members of this signaling pathway to block neuronal death has proved difficult, ATF2 offers a novel and promising alternative.
2025-04-30 | GSE282354 | GEO
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
2014-08-06 | GSE58734 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description: Not available
| S-EPMC4686780 | biostudies-literature
Project description: Not available
| S-EPMC3743458 | biostudies-literature
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress Keywords: other
2004-10-06 | GSE1810 | GEO
Project description: Not available
| S-EPMC5738339 | biostudies-literature
Project description:Reversible protein phosphorylation is one of the most important posttranslational modifications (PTMs) due to its vital role in cellular functions and signaling pathways. Protein phosphorylation is also known to be involved in the regulation of apoptosis. Previously, we have performed a SILAC-based analysis of phosphotyrosinylation of cisplatin-induced apoptotic Jurkat T cells. To further expand this study, we used the same experimental setup and analyzed the global phosphorylation profile. The different steps of the phosphopeptide enrichment protocol using TiO2 beads were tested and the best approach was applied in combination with LC-MS with different normalized collision energy (NCE) values for HCD fragmentation. In total, more than 2,000 phosphoproteins of more than 4,000 phosphopeptides were identified in the four biological replicates of both states. HCD with NCE 25 accounted for 64% and NCE 35 for 36 % of identified phosphopeptides. 425 phosphopeptides were found to be significantly regulated in cisplatin-treated against control samples. KEGG pathway analysis revealed splicosomal proteins and the MAPK signaling pathway to be upregulated and cell cycle proteins to be downregulated. The transcription factors Atf2 and Jun, which are both involved in the MAPK signaling pathway, were further investigated. For Jun, more than 90 spectral counts were found only in apoptotic cells and covered the well-known stress induced phosphorylation sites at S-63/S-73, as well as S-243 which reduces the ability to bind DNA and is required for GSK3 mediated ubiquitinylation at S-239. For Atf2, more than 60 spectral counts were found in apoptotic cells vs. 8 in control cells. Most significantly upregulated sites for Atf2 have been identified at S-90 and S-112, which are less well studied phosphorylation sites of Atf2 as several other sites. Western blot analyses using non-phosphorylated and phosphorylated antibodies were performed to validate the phosphorylation events of Jun and Atf2. Our findings contribute to the current knowledge of the phosphorylation profiles of apoptotic cells.
2017-05-11 | PXD004415 | Pride