Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Impact of Notch signaling on the TAF6delta-driven transcriptome.

ABSTRACT: TAF6delta, a pro-apoptotic transcription factor, induces a gene-expression signature that leads to cell death and upregulates genes in the Notch signaling pathway. To test the impact of Notch on the TAF6delta-driven transcriptome, we performed transcriptome profiling of HeLa cells in the presence of A Notch inhibitor of the gamma-secretase inhibitor class (S2188; CAS Number 200810-93-1; methyl (2S,3S)-2-[[(2S)-2-[[(4S)-2,2-difluoro-4-[[(2S,3S)-3-methyl-2-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-3-oxopentanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoate], a slice-site switching oligonucleotide targeting the TAF6 mRNA (SSO-TAF6delta) alone or in combination and compared those to vehicle (DMSO) treated cells. The three highest quality recordings from four biological replicates were used for further analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE313668 | GEO | 2026/01/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The plastidial Arabidopsis thaliana NFU1 delivers [4Fe-4S] clusters to specific client proteins

Project description:Proteins incorporating iron-sulfur (Fe-S) cofactors are required for a plethora of metabolic processes. Their maturation depends on three Fe-S cluster assembly machineries located in the cytosol, mitochondria and chloroplasts. After de novo formation on scaffold proteins, Fe-S centers are loaded on client proteins by use of Fe-S cluster transfer proteins. Among plastidial representatives of this latter category, NFU2 and NFU3 are required for the maturation of the [4Fe-4S] clusters found in photosystem I subunits acting upstream of HCF101. NFU2 is additionally required for the maturation of the [2Fe-2S] dihydroxyacid dehydratase, important for branched-chain amino acid synthesis. Here, we report that recombinant Arabidopsis thaliana NFU1 is able to solely assemble a [4Fe-4S] cluster per homodimer. We also provide insights into the specificity of NFU1 for the maturation of chloroplastic Fe-S proteins by performing co-immunoprecipitation experiments and assaying the physical interaction of NFU1 with many [4Fe-4S]-containing plastidial proteins using binary yeast two-hybrid assays. Interactions with two proteins involved in isoprenoid and thiamine biosynthesis, respectively 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (ISPG) and 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase (THIC), have been further confirmed by bimolecular fluorescence complementation and in vitro Fe-S cluster transfer experiments. The additional interactions detected with SUFD and SUFA allowed building a model in which NFU1 receives its Fe-S cluster from the SUFBC2D scaffold complex and serves for the maturation of [4Fe-4S] client proteins.

2020-07-06 | PXD015295 | Pride

TAF6 orchestrates transcription programs and apoptosis in the absence of p53

Project description:The decision of metazoan cells to live or undergo programmed cell death hinges on the balance between the levels of pro- versus anti-apoptotic gene products. The general RNA polymerase II (Pol II) transcription factor, TFIID, plays a central role in the regulation of gene expression through its core promoter recognition and co-activator functions. The core TFIID subunit TAF6 is a co-activator for the pro-apoptotic p53 tumour suppressor protein. Our previous studies identified a specialized isoform of TAF6, termed TAF6 that can specifically be induced in apoptosis. To elucidate the impact of TAF6 on gene expression and cell death, we employed modified antisense oligonucleotides to enforce expression of endogenous TAF6. The induction of endogenous TAF6 triggered apoptosis in several cancer cell lines. Importantly, TAF6 also induces apoptosis in tumor cell lines devoid of p53, placing TAF6 function downstream of p53. Microarray experiments uncovered a TAF6-induced transcriptome landscape displaying enhanced expression of genes of the Notch, oxidative stress, integrin, p53 and apoptosis pathways. Our data show that the TAF6 pathway is a pivotal signalling nexus that controls pro-apoptotic gene expression programs. Keywords: Treatment with splice site switching antisense oligonucleotides, induction of apoptosis Biological triplicates, 3 conditions: control oligonucleotide, Taf6 oligonucleotide, specificity control Bcl-x oligonucleotide

2010-11-27 | E-GEOD-8752 | biostudies-arrayexpress

TAF6 orchestrates transcription programs and apoptosis in the absence of p53

2010-11-27 | GSE8752 | GEO

Methyl-CpG-binding domain (MBD) sequencing of 15 primary stage 4S neuroblastoma tumors

Project description:The DNA methylome of 15 primary stage 4S neuroblastoma tumors is profiled by enrichment with a methyl-CpG-binding domain (MBD) and massively parallel sequencing

2015-12-15 | GSE69268 | GEO

Development of an Androgen Receptor Inhibitor Targeting the N-Terminal Domain of Androgen Receptor for Treatment of Castration Resistant Prostate Cancer

Project description:Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance occurs when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or when constitutively active splice variants lacking the androgen binding domain entirely (e.g. ARV7) is expressed. In this study, we are reporting the discovery of novel AR-NTD covalent inhibitor 1‐chloro‐3‐[(5‐([(2S)‐3‐chloro‐2‐hydroxypropyl]amino)naphthalen‐1‐yl)amino]propan‐2‐ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and its known coactivators and interactors, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. Taken together, our data suggest that VPC-220010 is a promising small molecule AR-NTD inhibitor for the treatment of CRPC.

2021-07-28 | GSE173331 | GEO

Fe-S clusters-binding proteins in mitoribosome

Project description:The human mitochondrial ribosome contains three [2Fe-2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play structural roles during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the expression of Fe-S cluster biosynthetic and delivery factors on mitoribosome stability. We have found that the mitoribosome receives its [2Fe-2S] clusters from the GLRX5-BOLA3. Additionally, the assembly of the small subunit depends on METTL17, recently reported to contain a [4Fe-4S] cluster, which we found to be inserted via ISCA1-NFU1. Consistently, fibroblasts from patients suffering from “multiple mitochondrial dysfunction” syndrome due to mutations in BOLA3 or NFU1 display previously unrecognized attenuation of mitochondrial protein synthesis that contributes to their cellular and pathophysiological phenotypes. Finally, we report that, in addition to their structural role, the mitoribosomal [2Fe-2S] clusters sense changes in the redox environment. In this way, the mitoribosome checks the availability and stability of mitochondrial Fe-S clusters to regulate organellar protein synthesis accordingly.

2024-01-26 | PXD039321 | Pride

Methyl-CpG-binding domain (MBD) sequencing of 15 primary stage 4S neuroblastoma tumors

Project description:The DNA methylome of 15 primary stage 4S neuroblastoma tumors is profiled by enrichment with a methyl-CpG-binding domain (MBD) and massively parallel sequencing DNA of 15 primary stage 4S tumors is sheared (fragments of Â± 200 bp), followed by MBD-based (MethylCap kit of Diagenode) enrichement, library preparation and multiplexing. Both input DNA and captured DNA were sequenced paired-end on Illumina Hiseq2000

2015-12-15 | E-GEOD-69268 | biostudies-arrayexpress

Assessment of tumour cell death with 68Ga Cell Death Indicator Positron Emission Tomography (68Ga-CDI PET): Proof of Concept

Project description:Interventions: Participants will be intravenously administered 1.8-2.2MBq/kg (maximum 220MBq) of [68Ga]gallium 2,2’-(7-(4-((1-carboxy-4-((1-((carboxymethyl)amino)-3-((2-((4-(dihydroxyarsaneyl)phenyl)amino)-2-oxoethyl)thio)-1-oxopropan-2-yl)amino)-4-oxobutyl)amino)-1-carboxylato-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetate (68Ga Cell Death Indicator [68Ga-CDI]) on two occasions, once within 14 days prior to commencing treatment and the second between day 15 and day 20 (inclusive) after commencement of treatment (chemoradiotherapy in the case of oesophageal / gastro-oesophageal and rectal carcinoma and chemotherapy in the case of breast carcinoma and lymphoma). One hour following each 68Ga-CDI administration, participants will undergo a positron emission tomography (PET) scan where they will lie still on a scanning bed (breathing normally). The scan will take approximately 30 minutes. 68Ga-CDI will be administered by a nuclear medicine specialist or medical radiation scientist. 68Ga-CDI administration and PET scannning will occur at the Prince of Wales Hospital, Randwick, NSW. Primary outcome(s): Tumour uptake of 68Ga-CDI assessed on PET scan.[Tumour uptake of 68Ga-CDI assessed on PET scan performed within 14 days prior to commencement of treatment and then again between 15 and 20 days after commencing treatment.] Study Design: Purpose: Diagnosis; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy

| 2472264 | ecrin-mdr-crc

Quantitative proteomic profiling of HCC1954 cells treated with a CDK12 degrader

Project description:HCC1954 cells growing at 80% confluency in a 10-cm dish were treated with (R)-2-(4-(9-ethyl-6-(((6-(furan-3-yl)pyridin-3-yl)methyl)amino)-9H-purin-2-yl)morpholin-3-yl)ethan-1-ol (a CDK12 degrader) at 300 nM (0.5% in DMSO) or DMSO as a control for 2 hours. Each was carried out in triplicates. The cells were disrupted in a lysis buffer containing 2% SDS, 2 mM MgCl2, 50 mM triethylammonium bicarbonate, 1x HALT phosphatase and protease inhibitors (ThermoFisher Scientific, Waltham, MA) using Bioruptor Sonicator (Diagenode, Denville, NJ). Proteins were recovered and proteolyzed with trypsin on S-trap columns (PROTIFI, Fairport, NY). The resultant peptides were labeled with 6-plex TMT isobaric reagents (triplicates for 2 conditions), mixed altogether, subfractionated by basic reversed phase high performance liquid chromatography, and analyzed by LC-MS/MS (ThermoFisher, Q-Exactive). The LC-MS/MS data were processed by using Proteome Discoverer v2.4.

2023-08-02 | MSV000092579 | MassIVE

Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1

Project description:High throughput screening and subsequent hit validation identified 4-isopropyl-3-(2-((1-phenylethyl) amino)pyrimidin-4-yl)oxazolidin-2-one as a potent inhibitor of IDH1R132H. Synthesis of the 4 separate diastereomers identified the (S,S)-diastereomer (IDH125) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs IDH1wt. Initial SAR exploration identified the key tolerances and potential for optimization. X-ray crystallography identified a functionally relevant allosteric binding site amenable to inhibitors which can penetrate the blood-brain barrier, and aided rational optimization. Potency improvement and modulation of the physico-chemical properties identified (S)-3-(2-(((S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethyl)amino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one (IDH889) with good in-vivo exposure and in-vivo activity in a mutant IDH1 xenograft mouse model. identified the (S,S)-diastereomer (IDH125) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs IDH1wt. Initial SAR exploration identified the key tolerances and potential for optimization. X-ray crystallography identified a functionally relevant allosteric binding site amenable to inhibitors which can penetrate the blood-brain barrier, and aided rational optimization. Potency improvement and modulation of the physico-chemical properties identified (S)-3-(2-(((S)-1-(5-(4-fluoro-3-methylphenyl)pyrimidin-2-yl)ethyl)amino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one (IDH889) with good in-vivo exposure and in-vivo activity in a mutant IDH1 xenograft mouse model

2016-09-01 | GSE85571 | GEO

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