Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

K48-Ubiquitin IP-MS of Jurkat leukemia cells treated with asparaginase

ABSTRACT: We have shown that drug-resistant leukemias rely on protein degradation through the ubiquitin proteasome pathway to survive during asparaginase therapy. Our studies support the model that this catabolic source of amino acids is upregulated in response to amino acid starvation. To investigate whether this involves bulk protein degradation or the degradation of specific protein targets, we analyzed K48-ubiquitinated proteins using immunoprecipitation with an anti-K48-linked ubiquitin antibody (Millipore #05-1307) followed by mass spectrometry proteomics from Jurkat cells after treatment with vehicle vs asparaginase. We found no enrichment of specific proteins after asparaginase treatment, consistent with the possibility that asparaginase therapy stimulates bulk protein degradation, although these results do not rule out degradation of specific proteins below the limit of detection of this assay.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Alejandro Gutierrez

PROVIDER: MSV000089226 | MassIVE | Fri Apr 08 11:57:00 BST 2022

SECONDARY ACCESSION(S): PXD033118

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

Project description:Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Yet, information on physiological roles and underlying signaling mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with a novel multiple congenital anomaly disorder caused by hemizygous variants in OTUD5, encoding a K48-/K63-linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of a select group of chromatin regulators. These include ARID1A/B, HDAC2, and HCF1, mutation of which underlie different developmental disorders that exhibit phenotypic overlap with OTUD5 patients. Consequently, loss of OTUD5 during early differentiation leads to less accessible chromatin at neuroectodermal enhancers and thus aberrant rewiring of gene expression networks. Our study describes a novel developmental disorder we name LINKED (LINKage-specific-deubiquitylation-deficiency-induced Embryonic Defects) syndrome, provides a previously unrecognized mechanistic link between phenotypically related diseases, and reveals linkage-specific ubiquitin cleavage from substrate groups (i.e. chromatin remodelers) as an essential mode of signaling required to coordinate embryonic differentiation pathways.

2020-11-02 | GSE160589 | GEO

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

2020-11-02 | GSE160588 | GEO

SUMOylation restrains the degradation of ACE2 through TOLLIP-mediated selective autophagy to facilitate the host susceptibility to SARS-CoV-2 infection

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) through a proteome-wide protein interaction analysis. We further demonstrate that E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. Pharmacological intervention of ACE2 SUMOylation blocks the entry of SARS-CoV-2 and viral infection-triggered immune responses. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.

2022-07-18 | GSE171130 | GEO

K48 ubiquitin selectively targets oxidized proteins in vivo

Project description:Ubiquitin is a highly conserved eukaryotic protein responsible for regulating a variety of functions when conjugated to target proteins. Ubiquitin is essential, accumulates during the stress response, and is the canonical signal for protein degradation by the proteasome. Still, the function of ubiquitin in response to oxidative stress, particularly in the removal of oxidized proteins remains elusive because of the number of potential targets and different roles that polyubiquitin chains can play. Since polyubiquitin chains linked by K48 ubiquitin are the most abundant and canonical signal for protein degradation, we investigated the roles of K48 ubiquitin in the degradation of oxidized proteins. Combining protein oxidation, linkage-specific ubiquitination screens, and quantitative proteomics, we found K48 ubiquitin accumulated in a bimodal fashion, at both the early and late phase of response. We further showed that a fraction of oxidized proteins are conjugated with K48 ubiquitin in vivo. Using quantitative proteomics we identified ~750 ubiquitinated proteins and ~400 oxidized proteins that were differentially modified during the stress response, and around half the proteins were both oxidized and ubiquitinated. These proteins were highly abundant and function in translation and energy metabolism. Finally, we showed that the ubiquitination system is required for degradation of oxidized proteins, suggesting that oxidized proteins that rapidly accumulate during stress are ubiquitinated, and degraded during the later recovery phase. This temporal disconnect may be necessary for reprogramming protein dynamics, restoring proteostasis, and resuming cell growth.

2021-04-30 | PXD014173 | Pride

Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency

Project description:Expression of the yeast Cth2 protein stimulates degradation of mRNAs encoding proteins with Fe-dependent functions in metabolism, in iron storage and in other cellular processes. We demonstrate that in response to Fe deprivation, the Cth2-homologue, Cth1, stimulates specific degradation of mRNAs involved in mitochondrially localized activities that include respiration and amino acid biosynthesis. Furthermore, yeast cells grown under Fe deprivation accumulate mRNAs encoding proteins that function in glucose metabolism. These studies demonstrate a reprogramming of cellular metabolism during Fe-starvation dependent on the coordinated activities of two mRNA binding proteins. Keywords: Messenger RNAs down regulated by Cth1 and Cth2 proteins in response to Fe-limitation

2008-07-15 | GSE11236 | GEO

Transcription profiling of S. cerevisiae cth1cth2 cells independently transformed with pRS416 (V), pRS416-CTH1 (C) or pRS416-CTH2 (T) reveals cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency

Project description:Expression of the yeast Cth2 protein stimulates degradation of mRNAs encoding proteins with Fe-dependent functions in metabolism, in iron storage and in other cellular processes. We demonstrate that in response to Fe deprivation, the Cth2-homologue, Cth1, stimulates specific degradation of mRNAs involved in mitochondrially localized activities that include respiration and amino acid biosynthesis. Furthermore, yeast cells grown under Fe deprivation accumulate mRNAs encoding proteins that function in glucose metabolism. These studies demonstrate a reprogramming of cellular metabolism during Fe-starvation dependent on the coordinated activities of two mRNA binding proteins. Experiment Overall Design: cth1cth2 cells independently transformed with pRS416 (V), pRS416-CTH1 (C) or pRS416-CTH2 (T) were grown in triplicate in SC-Ura containing 100 Î¼M BPS until exponential growth phase (approximately 6hrs) at 30 degrees, RNA was extracted using a standard glass beads protocol, labeled and hybridized to Yeast Genome S98 Afffymetrix arrays.

2008-10-20 | E-GEOD-11236 | biostudies-arrayexpress

Ubiquitin-dependent turnover of MYC promotes loading of the PAF complex on RNA Polymerase II to drive transcriptional elongation (ChIP-seq)

Project description:The MYC transcription factor is an unstable protein and its turnover is controlled by the ubiquitin system. Ubiquitination enhances MYC-dependent transactivation, but the underlying mechanism remains unresolved. Here we show that proteasomal turnover of MYC is dispensable for recruitment of RNA polymerase II (RNAPII), but is required to promote transcriptional elongation at MYC target genes. Degradation of MYC stimulates histone acetylation and recruitment of BRD4 and P-TEFb to target promoters, leading to phosphorylation of RNAPII CTD and the release of elongating RNAPII. In the absence of degradation, the RNA polymerase II-associated factor (PAF) complex associates with MYC via interaction of its CDC73 subunit with a conserved domain in the amino-terminus of MYC ("MYC box I"), suggesting that a MYC/PAF complex is an intermediate in transcriptional activation. Since histone acetylation depends on a second highly conserved domain in MYCs amino-terminus ("MYC box II"), we propose that both domains co-operate to transfer elongation factors onto paused RNAPII.

2016-01-04 | GSE70001 | GEO

Ubiquitin-dependent turnover of MYC promotes loading of the PAF complex on RNA Polymerase II to drive transcriptional elongation (RNA-seq)

2016-01-04 | GSE70000 | GEO

Ubiquitin-dependent turnover of MYC promotes loading of the PAF complex on RNA Polymerase II to drive transcriptional elongation (ChIP-seq)

2016-01-04 | E-GEOD-70001 | biostudies-arrayexpress

Selective Degradation of Splicing Factor CAPER-alpha by Anticancer Sulfonamides

Project description:Target protein degradation is an emerging field in drug discovery and development. In particular, the substrate receptor proteins of the cullin ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory drugs (IMiDs) represented by lenalidomide. Here, we demonstrate that a series of anticancer sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing factor CAPER-alpha via DCAF15-DDB1-CUL4 CRL4-DCAF15 mediated ubiquitination in human cancer cell lines. Both CRISPR/Cas9-based knockout of DCAF15 and a single amino acid substitution of CAPER-alpha conferred resistance against sulfonamide-induced CAPER-alpha degradation and cell-growth inhibition. Thus, the these sulfonamides represent selective chemical probes for disrupting CAPER-alpha function and designate DCAFs as promising drug targets for promoting selective protein degradation in cancer therapy.

2017-01-20 | GSE93829 | 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