Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human cancer cell proteomics identifies proteins that fail to be degraded upon treatment with a selective autophagy inhibitor

ABSTRACT: To identify the subproteome degraded by lysosomes in human cancer cells, we compared whole cell proteomes of wild-type and autophagy-deficient non-small cell lung cancer cells in the presence or absence of a lysosomal degradation inhibitor (N/L). Further, we compared whole cell proteomes of cells treated with a selective autophagy inhibitor in the presence or absence of N/L to identify lysosome substrate proteins that fail to be degraded upon treatment with this small molecule.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Simone Sidoli

LAB HEAD: Simone Sidoli

PROVIDER: PXD061323 | Pride | 2025-05-03

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20241214_Ellen_Olaya_C7-KD-1.raw	Raw
	20241214_Ellen_Olaya_C7-KD-2.raw	Raw
	20241214_Ellen_Olaya_C7-KD-3.raw	Raw
	20241214_Ellen_Olaya_C7-NL-KD-1.raw	Raw
	20241214_Ellen_Olaya_C7-NL-KD-2.raw	Raw

Items per page:

1 - 5 of 27

Similar Datasets

Chaperone-mediated autophagy sex-specifically regulates neuronal activity by remodeling the synaptic proteome

Project description:Chaperone-mediated autophagy (CMA) declines in aging and neurodegenerative diseases. CMA loss in neurons leads to neurodegeneration and behavioral changes in mice, but the role of CMA in neuronal physiology is largely unknown. Here, we show that CMA deficiency causes neuronal hyperactivity, disrupted calcium homeostasis and abnormally increased presynaptic neurotransmitter release in females and elevated postsynaptic AMPA signaling in males. Comparative quantitative proteomics revealed sexual dimorphism in the synaptic proteins degraded by CMA, with preferential remodeling of the presynaptic proteome in females and the postsynaptic proteome in males. We propose that impaired lysosomal degradation of these synaptic proteins may contribute to hyperexcitability in aging and neurodegeneration. Accordingly, we demonstrate that pharmacological CMA activation in an Alzheimer’s disease mouse model normalizes synaptic protein levels and neurotransmission. These findings unveil a role for CMA in the regulation of neuronal excitability and highlight this pathway as a potential target for mitigating age-related decline in neuronal function.

2025-09-04 | PXD057545 | Pride

Identification of sRNA binding to ITSmetZW and ITSmetWV using MS2-affinity purification coupled with RNA sequencing (MAPS) technology

Project description:During ribosomal and transfer RNA maturation, external transcribed spacer (ETS) and internal transcribed spacer (ITS) sequences are excised and, as non-functional by-products, are rapidly degraded. The 3’ETS of the glyW-cysT-leuZ polycistronic tRNA precursor was highly and specifically enriched by co-purification with at least two different small regulatory RNAs (sRNAs), RyhB and RybB. Both sRNAs were shown to base pair with the same region in the 3’ETS of leuZ (3’ETSleuZ). Disrupting the pairing by mutating 3’ETSleuZ significantly increased the activity of sRNAs, even under non-inducing conditions. Our results indicate that 3’ETSleuZ prevents sRNA-dependent remodeling of tricarboxylic acid (TCA) cycle fluxes and increases antibiotic sensitivity when sRNAs are transcriptionally repressed. This suggests that 3’ETSleuZ functions as a sponge to absorb transcriptional noise from repressed sRNAs. Finally, the fact that RybB and MicF sRNAs are co-purified with ITSmetZ-metW and ITSmetW-metV strongly suggests a much broader phenomenon. Identification of sRNAs co-purified with MS2-ITSmetZW and MS2-ITSmetWV. ITSmetZW and ITSmetWV (without MS2) were used as control

2015-04-16 | E-GEOD-66517 | biostudies-arrayexpress

Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy

Project description:This SuperSeries is composed of the following subset Series: GSE35701: CP001: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy GSE35703: CP003: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy Refer to individual Series

2012-07-21 | E-GEOD-35705 | biostudies-arrayexpress

Autophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 T cells - CTL data set

Project description:Autophagy is important for CD8 T-cells but autophagy timing, triggers and targets are poorly defined. Herein, we show naïve CD8-T cells have high autophagic flux and identify an autophagy checkpoint whereby antigen receptor engagement represses autophagy by regulating amino acid transporter expression and intracellular amino acid delivery. Effector cytotoxic T cells with high levels of amino acid transporters driven by proinflammatory cytokines have low autophagic flux but rapidly reinduce autophagy when amino acid restricted. A census of proteins degraded and fuelled by autophagy shows how autophagy shapes CD8-T cell proteomes. In cytotoxic T-cells, dominant autophagy substrates include cytolytic effector molecules, amino acid and glucose transporters. In naïve T-cells mitophagy dominates and selective mitochondrial pruning supports the expression of molecules that coordinate T-cell migration and survival. Autophagy thus differentially prunes naive and effector T-cell proteomes and is dynamically repressed by antigen receptors and inflammatory cytokines to shape T-cell differentiation.

2025-02-13 | PXD052733 | Pride

Autophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 T cells - IL7 data set

2025-02-13 | PXD052729 | Pride

CP003: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy

Project description:The PI3K-PKB/c-akt-FOXO signalling network provides a major intracellular hub for regulation of cell proliferation, survival and stress resistance1. Here we report a novel function for FOXO transcription factors in regulating autophagy through modulation of intracellular glutamine levels. To identify novel transcriptional targets of this module we performed an unbiased microarray analysis after conditional activation of the key components PI3K, PKB, FOXO3 and FOXO4. Utilising this global pathway approach we identified glutamine synthetase (GS) as being transcriptionally regulated by PI3K-PKB-FOXO signalling. FOXO-mediated increase in GS expression specifically induced glutamine production independently of cell type, and this was evolutionary conserved. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes, which was dependent on GS activity. Increased GS activity resulted in increased autophagosome turnover as measured by LC3 lipidation, p62 degradation, and confocal imaging of LC3, p62, WIPI-1, ULK2 and Atg12. Inhibition of FOXO3-mediated autophagy resulted in increased apoptosis, suggesting that the induction of autophagy by FOXO3-mediated upregulation of GS is important for cellular survival. These findings reveal a novel signalling network that can directly modulate autophagy through regulation of glutamine metabolism. conditional activation of foxo3 and foxo4 were followed in a timeseries. Each timepoint consists of 4 independent replicates, labeled with either cy3 or cy5 and put on array against time0 as reference.

2012-07-21 | E-GEOD-35703 | biostudies-arrayexpress

Autophagy driven by a master regulator of hematopoiesis

Project description:Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery function in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis GATA-1 directly activates transcription of genes encoding the essential autophagy component Microtubule Associated Protein 1 Light Chain 3B (LC3B) and its homologs (MAP1LC3A, GABARAP, GABARAPL1, GATE-16). In addition, GATA-1 directly activates genes involved in the biogenesis/function of lysosomes, which mediate autophagic protein turnover. We demonstrate that GATA-1 utilizes the forkhead protein FoxO3 to activate select autophagy genes. GATA-1-dependent LC3B induction is tightly coupled to accumulation of the active form of LC3B and autophagosomes, which mediate mitochondrial clearance as a critical step in erythropoiesis. These results illustrate a novel mechanism by which a master regulator of development establishes a genetic network to instigate cell type-specific autophagy. Genome-wide maps of GATA1 factor occupancy in primary human PBMC derived erythroblasts

2011-09-30 | E-GEOD-32491 | biostudies-arrayexpress

MS2-affinity purification coupled with RNA sequencing (MAPS) reveals RyhB sRNA targetome

Project description:Despite the overwhelming information about sRNAs, one of the biggest challenges in the sRNA field is characterizing sRNA targetomes. Thus, we develop a novel method to identify RNAs that interact with a specific sRNA, regardless of the type of regulation (positive or negative) or targets (mRNA, tRNA, sRNA). This method is called MAPS: MS2 affinity purification coupled with RNA sequencing. As proof of principle, we identified RNAs bound to RyhB, a well-characterized E. coli sRNA. Identification of RNAs co-purified with MS2-RyhB in a rne131 ?ryhB strain. RyhB (without MS2) was used as control

2015-04-16 | E-GEOD-66519 | biostudies-arrayexpress

Genomic Run-On (GRO): determination of the nascent transcriptional rate and mRNA amount in Xrn1 mutants

Project description:Maintaining the proper mRNA levels is a key aspect in the regulation of gene expression. The balance between mRNA synthesis and decay determines these levels. Using a whole-genome analysis, we demonstrate that most yeast mRNAs are degraded by the 5'-to-3' pathway (the "decaysome"), as proposed previously. Unexpectedly, the level of these mRNAs is highly robust to perturbations in this major pathway, as defects in various decaysome components lead to transcription down-regulation. Moreover, these components shuttle between the cytoplasm and the nucleus, in a manner dependent on proper mRNA degradation. In the nucleus, they associate with chromatin - preferentially ~30bp upstream of transcription start-sites - and directly stimulate transcription initiation and elongation. Hence, the decaysome has a dual role in maintaining mRNA levels. Significantly, proper import of some decaysome components seems to play a key role in coupling the two functions. The gene expression process is therefore circular, whereby the hitherto first and last stages are interconnected. This study focuses on the transcriptional activity of RNA pol II in 6035 S. cerevisiae ORFs. S. cerevisiae cells grown in YPD to exponential phase were subjected to Genomic Run-On. Data were normalized using gDNA hybridized on the same array and by the software ArrayStat. Home-made macroarrays containing 6035 ORFs were used.

2013-05-22 | E-GEOD-29519 | biostudies-arrayexpress

CP001: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy

Project description:The PI3K-PKB/c-akt-FOXO signalling network provides a major intracellular hub for regulation of cell proliferation, survival and stress resistance1. Here we report a novel function for FOXO transcription factors in regulating autophagy through modulation of intracellular glutamine levels. To identify novel transcriptional targets of this module we performed an unbiased microarray analysis after conditional activation of the key components PI3K, PKB, FOXO3 and FOXO4. Utilising this global pathway approach we identified glutamine synthetase (GS) as being transcriptionally regulated by PI3K-PKB-FOXO signalling. FOXO-mediated increase in GS expression specifically induced glutamine production independently of cell type, and this was evolutionary conserved. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes, which was dependent on GS activity. Increased GS activity resulted in increased autophagosome turnover as measured by LC3 lipidation, p62 degradation, and confocal imaging of LC3, p62, WIPI-1, ULK2 and Atg12. Inhibition of FOXO3-mediated autophagy resulted in increased apoptosis, suggesting that the induction of autophagy by FOXO3-mediated upregulation of GS is important for cellular survival. These findings reveal a novel signalling network that can directly modulate autophagy through regulation of glutamine metabolism. conditional activation of pkb and pi3k were followed in a timeseries. Each timepoint consists of 4 independent replicates, labeled with either cy3 or cy5 and put on array against time0.

2012-07-21 | E-GEOD-35701 | 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