Shigella induces stress granule formation by ADP-riboxanation of the eIF3 complex
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Xiaoyun Liu
PROVIDER: PXD048666 | iProX | Thu Jan 18 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:Chromatin ADP-ribosylation regulates important cellular processes. However, the exact location and magnitude of chromatin ADP-ribosylation are largely unknown. A robust and versatile method for assessing chromatin ADP-ribosylation is therefore crucial for further understanding its function. Here, we present a chromatin affinity precipitation method based on the high specificity and avidity of two well-characterized ADP-ribose binding domains to map chromatin ADP-ribosylation at the genome-wide scale and at specific loci. Our ADPr-ChAP method revealed that in cells exposed to oxidative stress, ADP-ribosylation of chromatin scaled with histone density, with highest levels at heterochromatic sites and depletion at active promoters. Furthermore, in growth factor-induced adipocyte differentiation, increased chromatin ADP-ribosylation was observed at PPARγ target genes, whose expression is ADP-ribosylation-dependent. In combination with deep-sequencing and conventional ChIP, the established ADPr-ChAP provides a valuable resource for the bioinformatic comparison of ADP-ribosylation with other chromatin modifications and for addressing its role in other biologically important processes.
2016-02-04 | GSE69885 | GEO
Project description:ADP-ribosylation is a common modification that occurs in proteins and nucleic acids, regulating many cellular processes ranging from DNA repair to inflammatory signaling. ADP-ribosylation plays an important role in cancer biology, infectious diseases, and obesity, but its role in the development of type 1 diabetes (T1D) is not well understood. Here, we studied the role of ADP-ribosyltransferase PARP12 in T1D development. PARP12 expression is highly induced in human islets treated with pro-inflammatory cytokines or β cells from diabetic donors. Proteomics analysis of MIN6 insulin-producing cells identified that the RNA machinery is regulated by PARP12 during inflammation. PARP12 also ADP-ribosylates 150 mRNAs, including the insulin mRNA. This mRNA ADP-ribosylation in turn modifies transcript localization and halts translation. Overall, our data identified a role for PARP12 in ADP-ribosylation and translation halting of mRNAs, which may affect insulin production during insulitis.
2025-03-28 | GSE292484 | GEO
Project description:Oxidative stress is a potent inducer of protein ADP-ribosylation. Although the proteins modified under oxidative stress have been identified, it is not clear, whether the number of modified proteins and/or the number ADP-ribosylation sites varies with stress intensity. Here, we investigated both the qualitative and quantitative changes in the HeLa cell ADP-ribosylome induced by mild (4 - 16 uM), moderate (64 - 250 uM), or severe, but non-lethal (1 mM) H2O2 concentrations using shotgun and parallel reaction monitoring mass spectrometry (PRM-MS). After moderate and severe oxidative stress, approximately 50% of proteins not ADP-ribosylated under basal conditions were induced, while ADP-ribosylation of the other 50% already ADP-ribosylated under basal conditions remained constant. In contrast, mild oxidative stress caused a reduction in detectable ADP-ribosylation of many proteins, which were induced under more severe oxidative stress. Overall, the number of ADP-ribosylation sites modified/de-modified did not change significantly under the various degrees of oxidative stress. Moreover, we applied the PRM method to study protein ADP-ribosylation in ovarian cancer cells that display different sensitivities to PARP inhibitors. These studies revealed similar ADP-ribosylation responses following H2O2 treatment, which, however, correlated in extent with ARTD1 abundance in these cells. Overall, our new MS approaches have proven to be highly useful in monitoring cellular protein ADP-ribosylation and have revealed unexpected fluctuations in proteins ADP-ribosylation depending on the degree of oxidative stress.
2016-11-13 | MSV000080334 | MassIVE
Project description:A key determinant of the pro-inflammatory responses in macrophages is the Signal Transducers and Activators of Transcription (STAT) family member, STAT1α. STAT1α activation by interferon-gamma (IFNγ) leads to induction of a transcriptional program that is coordinated in a large part by post-translational modifications such as phosphorylation. Poly(ADP-ribose) Polymerases (PARPs), which include PARP-1, catalyze the addition of ADP-ribose moieties (ADP-ribosylation) to target proteins and modulate their function. We found that PARP-1 mediates IFNγ-stimulated transcription by regulating genome-wide binding of STAT1α and its IFNγ-dependent phosphorylation. We identified STAT1α as a target of PARP-1 and found sites of ADP-ribosylation on its DNA-binding (DBD) and Transcription Activation (TA) domains. Surprisingly, ADP-ribosylation on the DBD and TA domains had distinct functional consequences on STAT1α transcriptional activity. Moreover, loss of ADP-ribosylation on either site led to diminished pro-inflammatory responses. These results suggest that PARP-1-driven ADP-ribosylation of STAT1α is a critical mediator of inflammation in macrophages.
2021-05-13 | GSE147959 | GEO
Project description:Mycobacterium tuberculosis maintains long-term infections characterised by the need to regulate growth and adapt to contrasting in vivo environments. Here we show that M. tuberculosis complex bacteria utilise reversible ADP-ribosylation of single-stranded DNA as an epigenetic mechanism to coordinate stationary phase growth with transcriptional adaptation. The DNA-modification is controlled by DarT, an ADP-ribosyl transferase, which adds ADP-ribose to thymidine, and DarG, which enzymatically removes this base modification. Using darG-knockdown M. bovis BCG, we map the first DNA-ADP-ribosylome from any organism. We show that inhibition of replication by DarT is reversible and accompanied by extensive ADP-ribosylation at the origin of replication (OriC). In addition, we observe ADP-ribosylation across the genome and demonstrate that ADP-ribose-thymidine alters the transcriptional activity of M. tuberculosis RNA polymerase. Furthermore, we demonstrate that during stationary phase, DarT-dependent ADP-ribosylation of M. tuberculosis DNA is required to optimally induce expression of the Zur regulon including the ESX-3 secretion system and multiple alternative ribosome proteins. Thus, ADP-ribosylation of DNA can provide an epigenetic link through every aspect of DNA biology from replication to transcription to translation.
2025-02-26 | GSE283124 | GEO
Project description:Mycobacterium tuberculosis maintains long-term infections characterised by the need to regulate growth and adapt to contrasting in vivo environments. Here we show that M. tuberculosis complex bacteria utilise reversible ADP-ribosylation of single-stranded DNA as an epigenetic mechanism to coordinate stationary phase growth with transcriptional adaptation. The DNA-modification is controlled by DarT, an ADP-ribosyl transferase, which adds ADP-ribose to thymidine, and DarG, which enzymatically removes this base modification. Using darG-knockdown M. bovis BCG, we map the first DNA-ADP-ribosylome from any organism. We show that inhibition of replication by DarT is reversible and accompanied by extensive ADP-ribosylation at the origin of replication (OriC). In addition, we observe ADP-ribosylation across the genome and demonstrate that ADP-ribose-thymidine alters the transcriptional activity of M. tuberculosis RNA polymerase. Furthermore, we demonstrate that during stationary phase, DarT-dependent ADP-ribosylation of M. tuberculosis DNA is required to optimally induce expression of the Zur regulon including the ESX-3 secretion system and multiple alternative ribosome proteins. Thus, ADP-ribosylation of DNA can provide an epigenetic link through every aspect of DNA biology from replication to transcription to translation.
2025-02-26 | GSE283123 | GEO
Project description:Mycobacterium tuberculosis maintains long-term infections characterised by the need to regulate growth and adapt to contrasting in vivo environments. Here we show that M. tuberculosis complex bacteria utilise reversible ADP-ribosylation of single-stranded DNA as an epigenetic mechanism to coordinate stationary phase growth with transcriptional adaptation. The DNA-modification is controlled by DarT, an ADP-ribosyl transferase, which adds ADP-ribose to thymidine, and DarG, which enzymatically removes this base modification. Using darG-knockdown M. bovis BCG, we map the first DNA-ADP-ribosylome from any organism. We show that inhibition of replication by DarT is reversible and accompanied by extensive ADP-ribosylation at the origin of replication (OriC). In addition, we observe ADP-ribosylation across the genome and demonstrate that ADP-ribose-thymidine alters the transcriptional activity of M. tuberculosis RNA polymerase. Furthermore, we demonstrate that during stationary phase, DarT-dependent ADP-ribosylation of M. tuberculosis DNA is required to optimally induce expression of the Zur regulon including the ESX-3 secretion system and multiple alternative ribosome proteins. Thus, ADP-ribosylation of DNA can provide an epigenetic link through every aspect of DNA biology from replication to transcription to translation.
2025-02-26 | GSE283122 | GEO
Project description:A key determinant of the pro-inflammatory responses in macrophages is the Signal Transducers and Activators of Transcription (STAT) family member, STAT1α. STAT1α activation by interferon-gamma (IFNγ) leads to induction of a transcriptional program that is coordinated in a large part by post-translational modifications such as phosphorylation. Poly(ADP-ribose) Polymerases (PARPs), which include PARP-1, catalyze the addition of ADP-ribose moieties (ADP-ribosylation) to target proteins and modulate their function. We found that PARP-1 mediates IFNγ-stimulated transcription by regulating genome-wide binding of STAT1α and its IFNγ-dependent phosphorylation. We identified STAT1α as a target of PARP-1 and found sites of ADP-ribosylation on its DNA-binding (DBD) and Transcription Activation (TA) domains. Surprisingly, ADP-ribosylation on the DBD and TA domains had distinct functional consequences on STAT1α transcriptional activity. Moreover, loss of ADP-ribosylation on either site led to diminished pro-inflammatory responses. These results suggest that PARP-1-driven ADP-ribosylation of STAT1α is a critical mediator of inflammation in macrophages.
2021-05-13 | GSE147951 | GEO
Project description:A key determinant of the pro-inflammatory responses in macrophages is the Signal Transducers and Activators of Transcription (STAT) family member, STAT1α. STAT1α activation by interferon-gamma (IFNγ) leads to induction of a transcriptional program that is coordinated in a large part by post-translational modifications such as phosphorylation. Poly(ADP-ribose) Polymerases (PARPs), which include PARP-1, catalyze the addition of ADP-ribose moieties (ADP-ribosylation) to target proteins and modulate their function. We found that PARP-1 mediates IFNγ-stimulated transcription by regulating genome-wide binding of STAT1α and its IFNγ-dependent phosphorylation. We identified STAT1α as a target of PARP-1 and found sites of ADP-ribosylation on its DNA-binding (DBD) and Transcription Activation (TA) domains. Surprisingly, ADP-ribosylation on the DBD and TA domains had distinct functional consequences on STAT1α transcriptional activity. Moreover, loss of ADP-ribosylation on either site led to diminished pro-inflammatory responses. These results suggest that PARP-1-driven ADP-ribosylation of STAT1α is a critical mediator of inflammation in macrophages.
2021-05-13 | GSE147952 | GEO
Project description:A key determinant of the pro-inflammatory responses in macrophages is the Signal Transducers and Activators of Transcription (STAT) family member, STAT1α. STAT1α activation by interferon-gamma (IFNγ) leads to induction of a transcriptional program that is coordinated in a large part by post-translational modifications such as phosphorylation. Poly(ADP-ribose) Polymerases (PARPs), which include PARP-1, catalyze the addition of ADP-ribose moieties (ADP-ribosylation) to target proteins and modulate their function. We found that PARP-1 mediates IFNγ-stimulated transcription by regulating genome-wide binding of STAT1α and its IFNγ-dependent phosphorylation. We identified STAT1α as a target of PARP-1 and found sites of ADP-ribosylation on its DNA-binding (DBD) and Transcription Activation (TA) domains. Surprisingly, ADP-ribosylation on the DBD and TA domains had distinct functional consequences on STAT1α transcriptional activity. Moreover, loss of ADP-ribosylation on either site led to diminished pro-inflammatory responses. These results suggest that PARP-1-driven ADP-ribosylation of STAT1α is a critical mediator of inflammation in macrophages.
2021-05-13 | GSE147955 | GEO