Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The translation termination factor GSPT1 is a phenotypically relevant off-target of heterobifunctional phthalimide degraders

ABSTRACT: The translation termination factor GSPT1 is a phenotypically relevant off-target of heterobifunctional phthalimide degraders

PROVIDER: PRJNA428512 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6493580.fastq.gz	Fastqsanger.gz
	SRR6493571.fastq.gz	Fastqsanger.gz
	SRR6493572.fastq.gz	Fastqsanger.gz
	SRR6493574.fastq.gz	Fastqsanger.gz
	SRR6493575.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 9

Similar Datasets

The translation termination factor GSPT1 is a phenotypically relevant off-target of heterobifunctional phthalimide degraders

Project description:Protein degradation is an emerging therapeutic strategy with a unique molecular pharmacology that enables the disruption of all functions associated with a target. This is particularly relevant for proteins depending on molecular scaffolding, such as transcription factors or receptor tyrosine kinases (RTKs). To address tractability of multiple RTKs for chemical degradation by the E3 ligase cereblon (CRBN), we synthesized a series of phthalimide degraders based on the promiscuous kinase inhibitors sunitinib and PHA665752. While both series failed to induce degradation of their consensus targets, individual molecules displayed pronounced efficacy in leukemia cell lines. Orthogonal target identification supported by molecular docking led us to identify the translation termination factor G1 to S phase transition 1 (GSPT1) as a converging off-target resulting from inadvertent E3 ligase modulation. This research highlights the importance of monitoring degradation events that are independent of the respective targeting ligand as a unique feature of small-molecule degraders.

2018-01-20 | GSE108763 | GEO

Functional TRIM24 degraders via conjugation of ineffectual bromodomain and VHL ligands [RNA-seq]

Project description:The addressable pocket of a target protein is often not functionally relevant. This is particularly true for multidomain gene regulatory proteins, such as the bromodomain-containing transcriptional regulator TRIM24. TRIM24 has been posited as a dependency in numerous human cancers, yet potent and selective ligands for the TRIM24 bromodomain do not exert effective anti-proliferative responses. We therefore repositioned these probes as targeting features for heterobifunctional protein degraders.

2018-03-05 | GSE100572 | GEO

Functional TRIM24 degraders via conjugation of ineffectual bromodomain and VHL ligands [ChIP-seq]

2018-03-05 | GSE100571 | GEO

Functional TRIM24 degraders via conjugation of ineffectual bromodomain and VHL ligands [RNA-Seq 2]

2018-03-05 | GSE106579 | GEO

Functional genomics identify distinct and overlapping genes mediating resistance to different classes of heterobifunctional degraders of oncoproteins

Project description:Heterobifunctional proteolysis-targeting chimeric compounds leverage the activity of E3 ligases to induce degradation of target oncoproteins and exhibit potent preclinical antitumor activity. To dissect the mechanisms regulating tumor cell sensitivity to different classes of pharmacological "degraders" of oncoproteins, we performed genome-scale CRISPR/Cas9-based gene-editing studies. We observed that myeloma cell resistance to "degraders" of different targets (BET bromodomain proteins, CDK9) and operating through CRBN (degronimids) or VHL is primarily mediated by prevention of, rather than adaptation to, breakdown of the target oncoprotein; involves loss-of-function for the cognate E3 ligase or interactors/regulators of the respective cullin-RING ligase (CRL) complex. The substantial gene-level differences for CRBN- vs. VHL-based degraders explains mechanistically the lack of cross-resistance for degraders targeting the same protein via different E3 ligase/CRLs.

2021-02-12 | GSE162205 | GEO

HCH degraders

Project description:Degraders od hexachlorocyclohexane from environmental samples from Egypt

| PRJEB6995 | ENA

A mini-hairpin shaped nascent peptide blocks translation termination by a distinct mechanism

Project description:The mini-hairpin shaped nascent peptide that blocks translation termination was found by comprehensive proteomics approach for small ORFs overexpression.

2025-02-17 | PXD052430 | JPOST Repository

PAHs and BTEX degraders

Project description:PAHs and BTEX degraders Metagenome

| PRJNA850664 | ENA

Electron acceptor-dependent identification of key anaerobic toluene degraders at a tar-oil contaminated aquifer by Pyro-SIP

Project description:Bioavailability of electron acceptors is probably the most limiting factor in the restoration of anoxic, contaminated environments. The oxidation of contaminants such as aromatic hydrocarbons, particularly in aquifers, often depends on the reduction of ferric iron or sulphate. We have previously detected a highly active fringe zone beneath a toluene plume at a tar-oil contaminated aquifer in Germany, where a specialized community of contaminant degraders co-dominated by Desulfobulbaceae and Geobacteraceae had established. Although on-site geochemistry links degradation to sulphidogenic processes, dominating catabolic (benzylsuccinate synthase alpha-subunit, bssA) genes detected in situ appeared more related to those of Geobacter spp. Therefore, a stable isotope probing (SIP) incubation of sediment samples with 13C7-toluene and comparative electron acceptor amendment was performed. We introduce pyrosequencing of templates from SIP microcosms as a powerful new strategy in SIP gradient interpretation (Pyro-SIP). Our results reveal the central role of Desulfobulbaceae for sulphidogenic toluene degradation in situ, and affiliate the detected bssA genes to this lineage. This, and the absence of 13C-labelled DNA of Geobacter spp. in SIP gradients preclude their relevance as toluene degraders in situ. In contrast, Betaproteobacteria related to Georgfuchsia spp. became labelled under iron-reducing conditions. Furthermore, secondary toluene degraders belonging to the Peptococcaceae detected in both treatments suggest the possibility of functional redundancy amongst anaerobic toluene degraders on site. 2 samples examined from the different electron-acceptors (sulphate or ferric iron) incubates at the time point of maximal toluene degradation.

2011-03-18 | E-GEOD-25449 | biostudies-arrayexpress

DNA-SIP ETBE degraders

Project description:Stable isotope profiling of ETBE degraders

| PRJEB52346 | ENA