Proteomics

Dataset Information

0

Ewing sarcoma protein-mediated regulation of poly(ADP-ribose) polymerase 1 dissociation

ABSTRACT: Poly(ADP-ribose) polymerase 1 (PARP1) critically facilitates DNA damage response (DDR) that suppresses genomic instability. However, the physiological function of PARP1 in regulating genomic integrity is unclear. We investigated the Ewing’s sarcoma breakpoint region 1 (EWS) and found that it regulated the physiological function of PARP1. EWS was indispensable to dissociation of PARP1 from damaged DNA, promoting DDR and regulating DDR protein expression. Abnormal PARP1 accumulation due to EWS expression silencing, induced hyper-PARylation, which exhausted cellular NAD+ levels and caused cell death in in vitro and in vivo. Positively charged EWS arginine-glycine-glycine (Arg-Gly-Gly, RGG) domains directly interact with poly ADP-ribose (PAR) chains produced by PARP1 and are essential to dissociate PARP1 from damaged DNA. Consistently, Ewing’s sarcoma cells with defective EWS function accumulated PARP1 on chromatin and tissues from Ewing’s sarcoma patients, exhibiting high PARylation levels. Taken together, loss of EWS causes defects in PARP1 dissociation and results in genomic instability.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Byung-gyu kim  

LAB HEAD: Kyungjae Myung

PROVIDER: PXD016145 | Pride | 2020-11-03

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
MPS_Mix_SILAC_quant_20170411_final.sf3 Other
mix_2fold_re.raw Raw
mix_2fold_rePD2.1.msf Msf
mix_2fold_rePD2.1.msf.mzid_mix_2fold_rePD2.1.msf.MGF Mzid
Items per page:
1 - 4 of 4
altmetric image

Publications

Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin.

Lee Seon-Gyeong SG   Kim Namwoo N   Kim Su-Min SM   Park In Bae IB   Kim Hyejin H   Kim Shinseog S   Kim Byung-Gyu BG   Hwang Jung Me JM   Baek In-Joon IJ   Gartner Anton A   Park Jun Hong JH   Myung Kyungjae K  

EMBO reports 20201001 11

Poly(ADP-ribose) polymerase 1 (PARP1) facilitates DNA damage response (DDR). While the Ewing's sarcoma breakpoint region 1 (EWS) protein fused to FLI1 triggers sarcoma formation, the physiological function of EWS is largely unknown. Here, we investigate the physiological role of EWS in regulating PARP1. We show that EWS is required for PARP1 dissociation from damaged DNA. Abnormal PARP1 accumulation caused by EWS inactivation leads to excessive Poly(ADP-Ribosy)lation (PARylation) and triggers ce  ...[more]

Similar Datasets

Proteomics An androgen signaling axis uses a writer and a reader of ADP-ribosylation to control protein complex assembly
2021-05-28 | PXD018811 | Pride
Proteomics An androgen signaling axis uses a writer and a reader of ADP-ribosylation to control protein complex assembly
2021-04-23 | PXD025195 | Pride
Proteomics SART1 modulates Poly-(ADP-Ribose) accumulation and PARP1 chromatin localization
2024-11-04 | PXD047970 | Pride
Proteomics pyruvate dehydrogenase kinase 4 regulate mitochondrial dynamics
2023-03-10 | PXD028379 | Pride
Proteomics An Archaeal Pilus Survives the Most Extreme Conditions Through Extensive Glycosylation
2020-05-26 | PXD012799 | Pride
Proteomics Proteomic Analysis of the IPF Mesenchymal Progenitor Cell Nuclear Proteome Identifies Abnormalities in Key Nodal Proteins That Underlie Their Fibrogenic Phenotype
2022-08-12 | PXD032352 | Pride
Transcriptomics EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development [gene expression]
2016-03-01 | E-GEOD-72704 | biostudies-arrayexpress
Genomics PARP1 expression drives the synergy between trabectedin and PARP1 inhibitors
2017-06-12 | GSE77175 | GEO
Transcriptomics PARP1 expression predicts and determines synergy between PARP1 inhibitors and trabectedin.
2017-06-12 | GSE76981 | GEO
Proteomics USP1 expression driven by EWS-FLI1 transcription factor stabilizes Survivin and promotes Ewing sarcoma cell survival
2024-01-26 | PXD041033 | Pride