PARP1-associated proteins identified by label-free quantitative mass spectrometry in HEK293T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Wenchu Lin
PROVIDER: PXD068168 | iProX | Mon Sep 08 00:00:00 BST 2025
REPOSITORIES: iProX
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Project description:Poly [ADP-ribose] polymerase 1 (PARP1) is involved in differentiation, proliferation, tumor transformation, in repair of single-stranded DNA and double-stranded DNA breaks (DSBs) in conjunction with BRCA. PARP1 enzyme works modifying nuclear proteins by poly ADP-ribosylation. It was found that PARP1 and HNRNPA2B1 bind at termini of forum domains and may play a role in coordinated regulation of genes in forum domains (Tchurikov et al., 2013). Forum domains are long DNA fragments of excised chromosomal DNA. Mostly forum domains are of 50-200 kb in length, although larger domains, up to 500 - 700 kb, are also observed. The domains are delimited by hot spots of double-strand breaks (DSBs). This ChIP-Seq is aimed to compare genome-wide binding sites of PARP1 with different genomic features, including the hot spots of DSBs.
2017-02-01 | GSE74954 | GEO
Project description:BACKGROUND & AIMS: The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate pro-inflammatory host gene response, which results in diarrheal disease. Several host factors are involved in the acute early response to Salmonella infection. Transcription factors and transcription co-regulators have an especially important function, because they are required for the expression and synthesis of pro-inflammatory cytokines, chemokines and adhesion molecules. A central transcription factor involved in inflammation is NF-κB, which requires the nuclear protein PARP1 as co-factor for the expression of some of its target genes. Here, we investigated the role of PARP1 during Salmonella infection using a mouse model for Salmonella-induced colitis. METHODS: To study enterocolitis by Salmonella Typhimurium, an established mouse model system, which relies on streptomycin-pretreatment prior to Salmonella infection, was employed. Histopathologic signs of inflammation and cecum colonization at various time-points after infection of wild type and PARP1 knockout mice were analyzed. PARP1 expression in the gut mucosa was studied by quantitative RT-PCR, Western blot and immunofluorescence. Gene expression profiles of infected and control infected mice in the wild type or PARP1 knockout background were obtained by whole mouse genome arrays and confirmed by quantitative RT-PCR. 2 genotypes (wildtype, PARP1 knockout), 2 treatments (Salmonella SB300 infection, Salmonella SB161 control infection), 2 time-points (6h, 10h). 2-3 replicates/condition.
2010-05-27 | E-GEOD-19174 | biostudies-arrayexpress
Project description:Trabectedin is a DNA-damaging agent with a peculiar mechanism of action; it traps the DNA repair machinery leading to DNA single- and double-strand breaks, particularly in BRCA1/2-deficient tumors. We hypothesized that trabectedin-induced DNA damage might activate PARP1 (a DNA-repair machinery key player), and consequently, PARP1 inhibition would perpetuate trabectedin-induced DNA damage. In several tumor histotypes, we demonstrated a different degree of synergism between trabectedin and PARP1 inhibitors (PARP1-Is). Independent of BRCA1/2 status, PARP1 expression dictated the degree of synergism. Namely, silenced PARP1 reduced trabectedin-PARP1-Is synergism, whereas overexpressed PARP1 increased combination efficacy. High-PARP1 expression and specific gene signatures associated with DNA damage response and repair (DDR-R) were predictive of trabectedin+PARP1-I synergy. These findings pave the way for the clinical development of this novel combination therapy, as well as evaluation of PARP1 expression and DDR-R signatures in tumor samples as predictive biomarkers of response
2017-06-12 | GSE77175 | GEO
Project description:Trabectedin is a DNA-damaging agent with a peculiar mechanism of action; it traps the DNA repair machinery leading to DNA single- and double-strand breaks, particularly in BRCA1/2-deficient tumors. We hypothesized that trabectedin-induced DNA damage might activate PARP1 (a DNA-repair machinery key player), and consequently, PARP1 inhibition would perpetuate trabectedin-induced DNA damage. In several tumor histotypes, we demonstrated a different degree of synergism between trabectedin and PARP1 inhibitors (PARP1-Is). Independent of BRCA1/2 status, PARP1 expression dictated the degree of synergism. Namely, silenced PARP1 reduced trabectedin-PARP1-Is synergism, whereas overexpressed PARP1 increased combination efficacy. High-PARP1 expression and specific gene signatures associated with DNA damage response and repair (DDR-R) were predictive of trabectedin+PARP1-I synergy. These findings pave the way for the clinical development of this novel combination therapy, as well as evaluation of PARP1 expression and DDR-R signatures in tumor samples as predictive biomarkers of response.
2017-06-12 | GSE76981 | GEO
Project description:Poly(ADP-ribose) polymerase 1 (PARP1) is a highly conserved nuclear protein in multicellular organisms that modulates chromatin opening, and by doing so, it plays a significant role in gene expression regulation during development and differentiation. Despite its significance, all reported Parp1 total knockout mice strains are viable and fertile with no developmental anomalies. It was previously believed that functional redundancy with other PARP family members explain such a controversy. PARP2 is the main candidate to fulfill PARP1 functions in Parp1 knockout mice. Indeed, Parp1 Parp2 double knockout mice are arrested early in development and unable to proceed through gastrulation. However, while PARP2 has similar catalytic domain to PARP1, it lacks other domains that play important regulatory roles, thus making the lack of developmental problems in Parp1 mice total knockouts highly unlikely. To address this question, we checked the best investigated and publicly available Parp1 knockout mice strain. We found that Parp1 is still expressed in these mice, based on the presence of its mRNA transcript. Contrary to prior assumptions, we identified persistent mRNA expression in knockout mice, albeit at reduced levels. Detailed transcript analysis revealed an alternatively spliced PARP1 variant lacking exon two with introduced artificial cassette. Subsequent protein analysis confirmed the existence of a truncated PARP1 protein in knockout mice. We established embryonic stem cell lines from knockout mice and revealed the presence of pADPr. The decreased level of pADPr was detected in knockout ES cells with Western Blotting analysis, but immunofluorescence staining didn’t detect any difference in distribution or level of pADPr in nuclei of knockout ES cells compared to control ones. Moreover, in double Parp1 Parg mutant ES cells the accumulation of pADPr greatly exceeded its amount in normal and even in hypomorph Parg mutant ES cells, suggesting the presence of functionally active PARP1. Therefore, our findings challenge the conventional understanding of PARP1 depletion effects.
2024-07-15 | GSE248429 | GEO
Project description:Poly-(ADP-ribose) polymerase inhibitors (PARPi) elicit anti-tumour activity in homologous recombination defective cancers by promoting cytotoxic, chromatin-bound, “trapped” PARP1 DNA lesions. How cells process trapped PARP1 remains unclear. By exploiting wild-type or trapping-resistant PARP1 transgenes combined with rapid immunoprecipitation mass-spectrometry of endogenous proteins (RIME) and Apex2-proximity labelling, we generated proteomic profiles of trapped and non-trapped PARP1 complexes. This combined approach identified an interaction between PARP1 and the ubiquitin system including its central component - the ubiquitin-regulated p97 ATPase (aka VCP).
2021-10-05 | PXD024337 | Pride
Project description:Focused PARP1 mutagenesis screen for talazoparib resistance in HeLa-PARP1-GFP and SUM149-GFP cells
| PRJEB24332 | ENA
Project description:Analysis of the role of PARP1 in gene transcription in MCF7 cells under non-stress conditions. The hypothesis was that PARP1 activity in MCF7 cells plays a role in gene transcription. The results indicate that PARP1 inhibition does not significantly affect transcription after 6 hours of treatment. Total RNA was collected from MCF7 cells that had been treated with ABT-888, PJ34, Olaparib, or DMSO for 6 hours.
2014-09-04 | E-GEOD-56400 | biostudies-arrayexpress
Project description:Poly(ADP-ribose) polymerases (PARPs) synthesize and bind branched polymers of ADP-ribose to acceptor proteins using NAD as a substrate, and participate to the control of gene transcription and DNA repair. PARP1, the most abundant isoform, regulates the expression of proinflammatory mediator - cytokines, chemokines and adhesion molecules, and inhibition of PARP1 enzymatic activity reduced or ameliorated autoimmune diseases in several experimental models, including colitis. However, the mechanism(s) underlying the protective effects of PARP1 inhibition in colitis and the cell types in which Parp1 deletion has the most significant impact are unknown. The objective of the current study was to determine the impact of Parp1 deletion on the innate immune response to mucosal injury. Genome-wide analysis of the colonic transcriptome was performed. Compared to WT, we demonstrated that Parp1-/-were protected from DSS-induced colitis and that this protection was associated with a dramatic transcriptional reprogramming in the colon. WT or Parp1-/- mice were treated with drinking water administered ad libitum without ot with 4% dextran sulfate (DSS) for seven days. Whole colon was collected for RNA extraction and hybridization on Affymetrix microarrays. Thee mice from each genotype/treatment groups were used in the analysis.
2016-01-08 | E-GEOD-76658 | biostudies-arrayexpress