Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNF25 provides tolerance towards chemotherapeutic mRNA damage

ABSTRACT: Many chemotherapeutic agents damage DNA, which is believed to mediate their therapeutic efficacy. However, most of these agents act pleiotropically and also damage RNA, raising questions about the contribution of RNA damage to therapeutic outcomes and whether cells possess factors that protect them from chemotherapeutic RNA damage. In this project, we compare the cellular response to azacytidine (azaC) and decitabine (azadC), two nucleoside analogues that are used to treat acute myeloid leukemia (AML). We uncovered that 5azaC induces RNA damage and triggers cell death through the integrated stress response, which is mediated by GCN1 and GCN2. We also identified the ubiquitin E3 ligases RNF25 as a specific resistance factor to 5azaC treatment. Combining ubiquitylome and phospho-proteome, we explore the underlying cellular signalling associated with 5azaC sensitivity and resistance

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Petra Beli

LAB HEAD: Prof. Dr. Petra Beli

PROVIDER: PXD059287 | Pride | 2026-03-14

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20231113_SFB1_PBE_ASR_Shubo_diGly_SILAC_C_5aC_RNF25KO5aC_Rep2_pH040.raw	Raw
	20231113_SFB1_PBE_ASR_Shubo_diGly_SILAC_C_5aC_RNF25KO5aC_Rep2_pH050.raw	Raw
	20231113_SFB1_PBE_ASR_Shubo_diGly_SILAC_C_5aC_RNF25KO5aC_Rep2_pH060.raw	Raw
	20231113_SFB1_PBE_ASR_Shubo_diGly_SILAC_C_5aC_RNF25KO5aC_Rep2_pH070.raw	Raw
	20231113_SFB1_PBE_ASR_Shubo_diGly_SILAC_C_5aC_RNF25KO5aC_Rep2_pH085.raw	Raw

Items per page:

1 - 5 of 63

Similar Datasets

High Mobility Group Box protein 3 (HMGB3) facilitates DNA interstrand crosslink processing and double-strand break repair in human cells

Project description:DNA damaging agents can contribute to genetic instability, and such agents are often used in cancer chemotherapeutic regimens due to their cytotoxicity. Thus, understanding the mechanisms involved in DNA damage processing can not only enhance our knowledge of basic DNA repair mechanisms, but may also be used to develop improved chemotherapeutic strategies to treat cancer. The high mobility group box protein 1 (HMGB1) is a known nucleotide excision repair (NER) co-factor, and its family member HMGB3 has been implicated in chemo-resistance in ovarian cancer. Here, we aim to understand the potential role(s) of HMGB3 in processing DNA damage. A potential role in NER was investigated using HMGB3 knockout human cell lines in response to UV damage. Interestingly, unlike HMGB1, HMGB3 does not appear to play a role in NER. Subsequently, potential roles in DNA interstrand crosslink (ICL) and DNA double-strand break (DSB) repair were investigated using mutagenesis assays, metaphase spreads, foci formation, a variety of DNA repair assays, and Tag-Seq analyses in human cells. We found evidence to suggest that HMGB3 is involved in the processing of both DSBs and ICLs in human cells. These novel results elucidate a role for HMGB3 in DNA damage repair, and surprisingly, also indicate a distinct role of HMGB3 in DNA damage repair from that of HMGB1. These findings advance our understanding of the role of HMGB3 in chemotherapeutic drug resistance and as a target for new chemotherapeutic strategies in the treatment of cancer.

2025-06-01 | GSE285696 | GEO

Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to Chromatin

Project description:Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stresses. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing to produce transcripts encoding two protein isoforms: a full-length protein and a shorter form lacking the N-terminal acidic domain. While the neuronal defects produced by total hnRNP R depletion have been investigated before, the individual functions of each hnRNP R isoforms are unknown. We generated a Hnrnpr knockout mouse (Hnrnprtm1a/tm1a) showing selective loss of the full-length hnRNP R isoform. Motoneurons cultured from Hnrnprtm1a/tm1a mice did not show any axonal growth defects. However, they show an accumulation of double-strand breaks and an impaired DNA damage response. Proteomic analysis of the hnRNP R interactome revealed the multifunctional Y-box binding protein 1 (Yb1) as a top interactor. Yb1 depleted motoneurons also exhibit defects in DNA ´damage repair. We show that Yb1 is recruited to chromatin upon DNA damage, a mechanism that is dependent on full length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.

2021-11-01 | PXD022467 | Pride

Dual protein kinase/ nucleoside kinase modulat ors for rationally designed polypharmacology

Project description:Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. A reverse proteomic approach has identified the target responsible for this sensitisation: the deoxycytidine kinase (dCK). Masitinib, as well as other protein kinase inhibitors such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation of nucleoside analogue drugs. This phenomenon leads to an increase of prodrug phosphorylation of most of the chemotherapeutic drugs activated by this nucleoside kinase. The unforeseen dual activity of protein kinase inhibition/nucleoside kinase activation could be of great therapeutic benefit, through either reducing toxicity of therapeutic agents by maintaining effectiveness at lower doses or by counteracting drug resistance initiated via down modulation of dCK target.

2017-11-13 | PXD007765 | Pride

Shotgun proteomic elucidation of Synergistic mechanisms of Cannabidiol and SN-38 in the MCF7 cells

Project description:We evaluted the synergyistic interactions of cannabidiol (CBD) with standard chemotherapeutic agents such as Docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-Ethyl-10-hydroxycamptothecin (SN38) in MCf7 cells ultising different synergy metrics. Then we explored the synergistic mechanisms on the proteome level of the most synergistic combination (CBD and SN38 in a molar ratio of 371:1, respectively)

2021-11-03 | PXD026587 | Pride

Early molecular assessment of osseointegration in humans

Project description:To determine the early temporal wide genome transcription regulation by the surface topography at the bone-implant interface of implants bearing micro-roughened or superimposed nanosurface topology. Fourty four cp titanium implants with surface topographies exhibiting nanoscale features (Osseospeed-OS) and microrough surface without nanoscale features (TiOblast-TiO) were placed in the alveolar bone of 11 systemically healthy subjects and subsequently harvested at 3 and 7 days after placement. Total RNA was isolated from cells adherent to retrieved implants. A whole genome microarray using the Affymetrix Human gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces.

2013-09-17 | E-GEOD-41446 | biostudies-arrayexpress

EGAS00001004581-13-sc-2024-02-13T10:05:09Z - samples

Project description:In developed countries, ~10% of individuals are exposed to systemic chemotherapy for cancer and other diseases. Many chemotherapeutic agents act by increasing DNA damage in cancer cells, hence triggering cell death. However, there is limited understanding of the extent and consequences of collateral DNA damage to normal tissues. To investigate the impact of chemotherapy on mutation burdens and cell population structure of a normal tissue we sequenced blood cell genomes from 23 individuals, aged 3-80 years, treated with a range of chemotherapy regimens. Substantial additional mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but there were differences in burden between different classes of agent, different agents of the same class and different blood cell types. Chemotherapy also induced premature changes in the cell population structure of normal blood, similar to those of normal ageing. The results constitute an initial survey of the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed during the course of their disease management, raising mechanistic questions and highlighting opportunities for mitigation of adverse effects.

| EGAD00001015339 | EGA

CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release

Project description:Cyclin-dependent kinase 7 (CDK7), part of the general transcription factor TFIIH, promotes gene transcription by phosphorylating the C-terminal domain of RNA polymerase II (RNA Pol II). Here, we combine rapid CDK7 kinase inhibition with multi-omics analysis to unravel the direct functions of CDK7 in human cells. CDK7 inhibition causes RNA Pol II retention at promoters, leading to decreased RNA Pol II initiation and immediate global downregulation of transcript synthesis. Elongation, termination, and recruitment of co-transcriptional factors are not directly affected. Although RNA Pol II, initiation factors, and Mediator accumulate at promoters, RNA Pol II complexes can also proceed into gene bodies without promoter-proximal pausing while retaining initiation factors and Mediator. Further downstream, RNA Pol II phosphorylation increases and initiation factors and Mediator are released, allowing recruitment of elongation factors and an increase in RNA Pol II elongation velocity. Collectively, CDK7 kinase activity promotes the release of initiation factors and Mediator from RNA Pol II, facilitating RNA Pol II escape from the promoter.

2024-05-31 | PXD037842 | Pride

DNA damage regulation and its role in drug-related phenotypes in the malaria parasites. [genomic DNA]

Project description:The goal of our study is to characterize the global transcriptional resposne of P.falciparum to DNA damageing agents. Alongside, we stidied the epigenetic regulation of DNA damage resposne in parasite. Further, we studied the mecanism which underlined the ARMD (mutator) phenotype of P. falciparum. In order to elucidate the transcriptiona resposne to DNA damage, P. falciparum 3D7 parasites were treated with 4 perturbating agents for 6 hours. We mapped the global nucleosome occupancy for 3 most responsive histone modifications to DNA damage by chromatin immunoprecipitation coupled with DNA microarray (ChIP-on-chip). In order to identify the transcriptional similarities between artemesinin and MMS, we carried out 6 hours of artemesinin treatment in triplicates and compared with triplicate dataset of MMS.

2016-06-01 | E-GEOD-72579 | biostudies-arrayexpress

Targeting cholesterol homeostasis eliminates drug-tolerant persister cells in glioblastoma

Project description:The transition of cancer cells between drug-sensitive and drug-tolerant persister phenotypes drives treatment failures. Using glioblastoma models, we identified MRK-740, an inhibitor of H3K4 methyltransferase PRDM7/9, as a potent enhancer of chemotherapy-induced cell death, resulting in elimination of glioblastoma persister cells. Mechanistic investigations as well as analysis of glioblastoma specimens revealed that H3K4me3 is a transcription-activating mark at the promoters of key genes involved in cholesterol biosynthesis. The inhibition of H3K4 methylation in cells treated with microtubule-targeting agents led to the disruption of cholesterol homeostasis and LXR-dependent cholesterol efflux, ultimately depleting intracellular cholesterol and causing the death of persisters. Furthermore, we have developed a brain permeable microtubule-targeting agent to validate these mechanistic findings in vivo. We show that a combination of our novel chemotherapeutic agent and a brain permeable LXR agonist significantly extends survival in a glioblastoma mouse model. These results uncover the importance of balanced cholesterol homeostasis in chemotherapy tolerance.

2025-12-22 | PXD050643 | Pride

HDAC and aminopeptidase inhibitor treatment of myeloma cells

Project description:H929 human myeloma cells were exposed to aminopeptidase inhibitor (CHR-2797), HDAC inhibitor (CHR-3996), or a combinaion of the two agents, for 24 hours. Following this treatment RNA was extracted and microarrays used to determine gene expression changes. Myeloma cells were exposed to chemotherapeutic agent for 24 hours.

2014-01-24 | E-GEOD-20405 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data