Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD004255
PROVIDER: PRJNA392173 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here, we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light, and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA binding proteins as primary substrates and 14-3-3 as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Mechanistically, we show that MK2 phosphorylates the RNA binding subunit of the NELF complex NELFE on Serine 115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin, which is accompanied by RNA polymerase II elongation.
2018-02-08 | GSE100580 | GEO
Project description:Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that interfere with replication and transcription. Recent studies showed that exposure of human cells to UV light globally affects transcription and alternative splicing, however, the signaling pathways and mechanisms that link UV light-induced DNA damage to RNA metabolism regulation remain poorly understood. Here, we provide a systems view on protein phosphorylation patterns induced by UV light, and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling mediated by ATM/ATR or p38 MAP kinase pathway. We identify RNA binding proteins as primary targets and 14-3-3 family as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Moreover, we show that MK2 phosphorylates the RNA binding subunit of the NELF complex NELFE on S115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin that is accompanied with an increase in transcriptional elongation.
2018-02-09 | PXD004255 | Pride
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355007 | ENA
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355010 | ENA
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355009 | ENA
Project description:Ultraviolet (UV) light induces the formation of bulky UV photoproducts in the genome that interfere with DNA replication and transcription. It is well-established how human cells repair UV light-induced DNA lesions, however the signaling pathways and mechanisms that regulate transcription after exposure to UV light are poorly understood. Here, we provide a systematic view on dynamic protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on canonical DNA damage kinases and the p38 MAP kinase pathway. Notably, we demonstrate that p38 and its downstream effector kinase MK2 are responsible for one quarter of protein phosphorylation induced by UV light. We identify RNA binding proteins as primary targets and 14-3-3 family proteins as direct readers of UV light-induced, p38-MK2-dependent phosphorylation. Importantly, we demonstrate that UV light triggers rapid and dynamic phosphorylation of the negative elongation factor (NELF) complex subunit NELFE on serine 115 that mediates its binding to 14-3-3. NELFE interaction with 14-3-3 stabilizes NELFE and RNA pol II interaction on the chromatin and inhibits transcriptional elongation, thereby promoting cell survival after UV light.
2019-11-24 | GSE90555 | GEO
Project description:Ultraviolet (UV) light induces the formation of bulky UV photoproducts in the genome that interfere with DNA replication and transcription. It is well-established how human cells repair UV light-induced DNA lesions, however the signaling pathways and mechanisms that regulate transcription after exposure to UV light are poorly understood. Here, we provide a systematic view on dynamic protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on canonical DNA damage kinases and the p38 MAP kinase pathway. Notably, we demonstrate that p38 and its downstream effector kinase MK2 are responsible for one quarter of protein phosphorylation induced by UV light. We identify RNA binding proteins as primary targets and 14-3-3 family proteins as direct readers of UV light-induced, p38-MK2-dependent phosphorylation. Importantly, we demonstrate that UV light triggers rapid and dynamic phosphorylation of the negative elongation factor (NELF) complex subunit NELFE on serine 115 that mediates its binding to 14-3-3. NELFE interaction with 14-3-3 stabilizes NELFE and RNA pol II interaction on the chromatin and inhibits transcriptional elongation, thereby promoting cell survival after UV light.
2019-11-24 | GSE90554 | GEO
Project description:Cockayne syndrome B (CSB) protein is a member of the SWI/SNF family and has DNA-dependent ATPase and ATP-dependent chromatin remodeling activities. The CSB protein is missing or altered in CS-B cells. CS-B cells are hypersensitive to UV light and defective in transcription-coupled DNA repair (TCR). TCR efficiently removes a variety of lesions from the transcribed strand of active genes. It has been shown that lesions specifically in the transcribed strand of active genes trigger the induction of apoptosis following UV irradiation. Several DNA damage signaling cascades, including the ATR/Chk1, p38 kinase, p53, and jun N-terminal kinase pathways are activated following UV irradiation. However, the role of TCR in cellular global transcriptional responses to UV irradiation remains to be elucidated. Using oligonucleotide microarray technology, we analyzed the time course of responses of CS-B cells (CS-B) and CS-B cells complemented with wild-type CSB cDNA (CS-B wt). Experiment Overall Design: In order to investigate the global transcriptional responses to UV damage in TCR-proficient or TCR-deficient cells, CS-B wt and CS-B cells were irradiated with 10 J/m2 of UV light and incubated for 2 or 12 hours. All experiments were performed in triplicate.
2008-06-17 | E-GEOD-8939 | biostudies-arrayexpress
Project description:The effects of UV light on the skin have been extensively investigated. However, systematic information about how exposure to UVA light, the least energetic but the most abundant UV radiation reaching the Earth, shapes the subcellular organization of proteins is lacking. Using subcellular fractionation, mass-spectrometry-based proteomics, machine learning algorithms, immunofluorescence, and functional assays, we mapped the subcellular reorganization of the proteome of human keratinocytes in response to UVA light. Our workflow quantified and assigned subcellular localization and redistribution patterns for over 3000 proteins, of which about 600 were found to redistribute upon UVA exposure. Reorganization of the proteome affected modulators of signaling pathways, cellular metabolism and DNA damage response. Strikingly, mitochondria were identified as the main target of UVA-induced stress. Further investigation demonstrated that UVA induces mitochondrial fragmentation, up-regulates redox-responsive proteins and attenuates respiratory rates. These observations emphasize the role of this radiation as a potent metabolic stressor in the skin.
2022-03-06 | PXD027941 | Pride
Project description:Cockayne syndrome B (CSB) protein is a member of the SWI/SNF family and has DNA-dependent ATPase and ATP-dependent chromatin remodeling activities. The CSB protein is missing or altered in CS-B cells. CS-B cells are hypersensitive to UV light and defective in transcription-coupled DNA repair (TCR). TCR efficiently removes a variety of lesions from the transcribed strand of active genes. It has been shown that lesions specifically in the transcribed strand of active genes trigger the induction of apoptosis following UV irradiation. Several DNA damage signaling cascades, including the ATR/Chk1, p38 kinase, p53, and jun N-terminal kinase pathways are activated following UV irradiation. However, the role of TCR in cellular global transcriptional responses to UV irradiation remains to be elucidated. Using oligonucleotide microarray technology, we analyzed the time course of responses of CS-B cells (CS-B) and CS-B cells complemented with wild-type CSB cDNA (CS-B wt). Keywords: UV response, time course, disease state analysis
2007-09-10 | GSE8939 | GEO