P38-MK2 regulate RNA metabolism after UV light-induced DNA damage
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ABSTRACT:
PROVIDER: PRJNA355007 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5058060.fastq.gz | Fastqsanger.gz | |||
| SRR5058070.fastq.gz | Fastqsanger.gz | |||
| SRR5058061.fastq.gz | Fastqsanger.gz | |||
| SRR5058071.fastq.gz | Fastqsanger.gz | |||
| SRR5058052.fastq.gz | Fastqsanger.gz |
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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: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 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:This SuperSeries is composed of the SubSeries listed below.
2019-11-24 | GSE90556 | GEO
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355009 | ENA
Project description:p38-MK2 regulate RNA metabolism after UV light-induced DNA damage
| PRJNA355010 | ENA
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.
| S-EPMC5845016 | biostudies-literature
Project description:p38-MK2 signaling axis regulates RNA metabolism after UV light-induced DNA damage
| PRJNA392173 | ENA
Project description:Maintenance of lysosomal integrity is essential for cell viability. Upon injury, lysosomes may be targeted for degradation via a form of selective autophagy known as lysophagy, in which autophagosomes engulf damaged lysosomes following the recruitment of adaptor proteins. One of these adaptors, SQSTM1/p62, promotes lysophagy via liquid-like phase separation on damaged lysosomes. The formation of p62 condensates is regulated by the heat shock protein HSP27. Here, we demonstrate a direct interaction between HSP27 and p62. We used structural modeling to predict the binding interface between HSP27 and p62, and found several disease-associated mutations that map to this interface and disrupt the interaction. We then used proteomics to identify post-translational modifications of HSP27 that determine HSP27 recruitment to stressed lysosomes, finding robust phosphorylation at Serine residues 15, 78, and 82. We characterized the signaling mechanism leading to HSP27 phosphorylation. We find that p38 MAPK and its effector kinase MK2 are activated upon lysosomal damage by the kinase mTOR and the production of intracellular reactive oxygen species (ROS). Increased ROS activates p38 MAPK, which in turn allows MK2-dependent phosphorylation of HSP27. Either depletion of HSP27 or inhibition of HSP27 phosphorylation alters the liquidity of p62 condensates, significantly inhibiting p62-dependent lysophagy. Thus, we define a novel lysosomal quality control mechanism in which lysosomal injury triggers a p38 MAPK/MK2 signaling cascade regulating p62-dependent lysophagy. Further, this signaling cascade is activated by a variety of cellular stressors, including oxidative and heat stress, suggesting that other forms of selective autophagy may be regulated by p38 MAPK/MK2/HSP27.
2024-10-22 | PXD051927 | Pride