Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

K6-Linked Ubiquitylation Signals Reactive Aldehyde-Induced RNA-Protein Crosslink Resolution

ABSTRACT: Reactive aldehydes induce the formation of RNA-protein crosslinks (RPCs), RPCs in the mRNA stall the ribosome and inhibit translation, RPCs are K6-linked ubiqutylated by RBR-type E3 ligase RNF14, RPCs are resolved in a UBXN1-VCP/p97-dependent manner

ORGANISM(S): Homo sapiens

PROVIDER: GSE240625 | GEO | 2023/11/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

K6-Linked Ubiquitylation Marks Formaldehyde-Induced RNA–Protein Crosslinks for Resolution

Project description:Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces RNA–protein crosslinks (RPCs) that stall the ribosome and inhibit translation in human cells. RPCs in the messenger RNA are recognized by the translating ribosomes, marked by atypical K6-linked ubiquitylation catalyzed by the RING-in-Between-RING E3 ligase RNF14, and subsequently resolved by the ubiquitin- and ATP-dependent unfoldase VCP. Our findings uncover an evolutionary conserved formaldehyde-induced stress response pathway that protects cells against RPC accumulation in the cytoplasm, and suggest that RPCs contribute to the cellular and tissue toxicity of reactive aldehydes.

2023-11-13 | PXD038655 | Pride

Atypical K6-linked ubiquitylation marks toxic RNA-protein crosslinks induced by formaldehyde

Project description:Reactive aldehydes are produced during cellular metabolism and can accumulate in specific tissues particularly when aldehyde clearance mechanisms are impaired. Reactive aldehydes induce DNA-DNA and DNA-protein crosslinks (DPCs) that are repaired by different DNA repair pathways. Cellular toxicity of endogenous formaldehyde has been attributed to the damage of the genomic DNA and consequent inhibition of transcription. However, whether damage to other cellular macromolecules and interference with additional metabolic processes contributes to formaldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces toxic RNA-protein crosslinks (RPCs) in mRNA that inhibit translation and induce a specific RPC stress response pathway that is characterized by linkage-specific ubiquitylation. RPCs in the mRNA are recognized by stalling ribosomes and marked by K6-linked ubiquitylation that promotes their clearance by the ubiquitin-dependent unfoldase VCP.

2023-09-01 | GSE225044 | GEO

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

Project description:VCP is an evolutionary conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the substrate spectrum of VCP in human cells. We demonstrate that inhibition of VCP perturbs cellular ubiquitylation and increases ubiquitylation of a different subset of proteins compared to proteasome inhibition. VCP inhibition globally upregulates K6-linked ubiquitylation that is dependent on the HECT-type ubiquitin E3 ligase HUWE1. We report ~450 putative VCP substrates, many of which function in nuclear processes, including gene expression, DNA repair and cell cycle. Moreover, we identify that VCP regulates the level and activity of the transcription factor c-Myc.

2018-02-08 | GSE107313 | GEO

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

2018-02-09 | PXD003936 | Pride

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

Project description:Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function

| PRJNA419745 | ENA

The differentiation/retrodifferentiation program of human U937 leukemia cells is accompanied by changes of VCP/p97

Project description:A possible functional role of VCP/p97 during differentiation of U937 cells was addressed by siRNA-targeting of VCP/p97. Functional changes in VCP-siRNA-transfected cells following phorbol ester-induced monocytic differentiation have been examind by DNA microarray analysis. Cells transfected with the non-targeting AllStars negative siRNA (Qiagen) served as a reference. Computed

2010-06-29 | E-GEOD-9821 | biostudies-arrayexpress

K6-Linked Ubiquitylation Signals Reactive Aldehyde-Induced RNA-Protein Crosslink Resolution

Project description:K6-Linked Ubiquitylation Signals Reactive Aldehyde-Induced RNA-Protein Crosslink Resolution

| PRJNA1004331 | ENA

The differentiation/retrodifferentiation program of human U937 leukemia cells is accompanied by changes of VCP/p97

2008-01-23 | GSE9821 | GEO

RNAi knock down of VCP in human HeLa cells

Project description:Study of the effects of the VCP knockdown. VCP (p97, yeast cdc48) is a hexameric AAA ATPase involved in various cellular functions including degradation of proteins by the ubiquitin-proteasome system. We examine the consequences of the reduction of VCP levels after RNAi of VCP in HeLa cells. We find ~30 transcripts upregulated in a sequence independent manner. Those transcripts encode proteins involved in endoplasmic reticulum stress, apoptosis, and amino acid starvation.

2006-08-23 | E-MEXP-817 | biostudies-arrayexpress

ASPSCR1-TFE3 reprograms transcription by organizing enhancers around hexameric VCP [Cell_lines_ChIP, FUUR1, FUUR1_VCP]

Project description:ChIPseq experiments identify that ASPSCR1-TFE3 defines active enhancers across the genome and co-distributes with VCP/p97. RNAseq after knock-down of ASPSCR1-TFE3 or VCP, inhibition of VCP, or overexpression of each in alveolar soft part sarcoma cell lines demonstrates their co-dependence. HiChIP defines chromatin conformations that surround ASPSCR1-TFE3 targets and are lost on VCP knock-down.

2023-01-01 | GSE162482 | 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