Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pex39 facilitates peroxisomal import of PTS2 proteins – PEX39 KO SILAC data

ABSTRACT: Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (peroxins/PEXs) cause devastating disease. PEX7 binds cargo proteins containing a type 2 peroxisomal targeting sequence (PTS2) to enable import of PTS2 proteins from the cytosol into peroxisomes. However, many aspects of PTS2-protein import remain enigmatic. Utilizing in vitro assays, yeast, and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates PTS2-protein import by binding PEX7 and stabilizing its interaction with PTS2 cargo. PEX39 and the N-terminus of PEX13, a peroxisomal membrane translocon protein, both possess a KPWE motif necessary for PEX7 binding. Sequential binding of PEX7 to this motif in PEX39 and PEX13 provides a novel paradigm for how PTS2 cargo engage the translocation machinery. Collectively, our work uncovers an ancient and functionally important relationship among PEX39, PEX7, and PEX13, offering insights that will advance our understanding of peroxisomal disease.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Julian Bender

LAB HEAD: Bettina Warscheid

PROVIDER: PXD051550 | Pride | 2025-07-07

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	QEplus035022.raw	Raw
	QEplus035023.raw	Raw
	QEplus035024.raw	Raw
	QEplus035025.raw	Raw
	QEplus035027.raw	Raw

Items per page:

1 - 5 of 33

Similar Datasets

Pex39 facilitates peroxisomal import of PTS2 proteins – ScPex18 AP-MS data

Project description:Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (peroxins/PEXs) cause devastating disease. PEX7 binds cargo proteins containing a type 2 peroxisomal targeting sequence (PTS2) to enable import of PTS2 proteins from the cytosol into peroxisomes. However, many aspects of PTS2-protein import remain enigmatic. Utilizing in vitro assays, yeast, and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates PTS2-protein import by binding PEX7 and stabilizing its interaction with PTS2 cargo. PEX39 and the N-terminus of PEX13, a peroxisomal membrane translocon protein, both possess a KPWE motif necessary for PEX7 binding. Sequential binding of PEX7 to this motif in PEX39 and PEX13 provides a novel paradigm for how PTS2 cargo engage the translocation machinery. Collectively, our work uncovers an ancient and functionally important relationship among PEX39, PEX7, and PEX13, offering insights that will advance our understanding of peroxisomal disease.

2025-07-07 | PXD051501 | Pride

Peroxisomal retrograde signaling in C. elegans

Project description:Distinct retrograde signaling pathways have been identified for several cellular organelles. These pathways are important to maintain the function of these organelles in response to organelle-specific stress. Using Caenorhabditis elegans, we show for the first time that such a retrograde signaling also exists for peroxisomes. Analysis of the C. elegans transcriptome revealed that peroxisomal import stress caused by the knock-down of the peroxisomal matrix protein import receptor prx-5/PEX5 induces the compensatory up-regulation of genes involved in defense response and lipid metabolic processes, especially peroxisomal beta oxidation. We, therefore, propose that the peroxisomal retrograde signaling participates in the maintenance of peroxisomal function in response to peroxisomal import stress.

2020-12-19 | GSE156318 | GEO

Mitoprotein-induced stress launches a global transcriptional fail-safe program

Project description:Most mitochondrial proteins are synthesized as cytosolic precursor proteins before being imported into mitochondria. Cytosolic accumulation of mitochondrial precursors hazards cellular fitness and is associated with a growing number of diseases, but is not observed under physiological conditions. Individual mechanisms that allow cells to avoid cytosolic accumulation of mitochondrial precursors have recently been discovered, but their interplay and regulation remain elusive. Here we show that cells rapidly launch a global transcriptional program to restore cellular proteostasis after induction of a “clogger” protein that reduces the number of available mitochondrial import sites. Cells upregulate the protein folding and proteolytic systems in the cytosol and downregulate both the cytosolic translation machinery and many mitochondrial metabolic enzymes, presumably to relieve the workload of the overstrained mitochondrial import system. We show that this transcriptional remodeling is a combination of a “wideband” core response regulated by the transcription factors Hsf1 and Rpn4 and a unique mitoprotein-induced downregulation of the oxidative phosphorylation components, the most abundant group of precursorsmediated by an inactivation of the Hap2/3/4/5 complex. These findings depict the first comprehensive, time-resolved model of adaptations to mitochondrial import impairment. This reveals the regulation of previously described reactions and combines them with a so far unidentified mitochondrion-specific arm into an overarching coordinated network of the cellular mitoprotein-induced stress response.

2019-01-14 | PXD011789 | Pride

Global proteomics analysis of Saccharomyces WT versus PEX3 knockout cells

Project description:Peroxisomes are common eukaryotic cell organelles. So far, the inventory of the yeast peroxisomal proteome is still incomplete. To identify novel peroxisomal proteins, we compared yeast wild-type (WT) and PEX3 knockout cells, which lack functional peroxisomes by whole cell proteomics and transcriptomics. Cells were grown on acetate, a carbon source that involves peroxisomal enzymes of the glyoxylate cycle. Transcriptome analysis showed that, with the exception of transcripts of β-oxidation enzymes, the transcriptome of peroxisomal proteins was largely unchanged. In contrast, whole cell proteomics analysis revealed that peroxisome deficiency results in a reduction of the levels of peroxisomal membrane proteins. A set of non-peroxisomal membrane proteins showed a similar behavior. We therefore analyzed one of these proteins, the mitochondrial pyruvate carrier protein Mpc3, and show that Mpc3 has a dual localization on peroxisomes and mitochondria. In conclusion we present a novel approach to uncover new examples of dually localized membrane proteins.

2025-02-21 | PXD047234 | Pride

Towards the molecular architecture of the peroxisomal receptor docking complex

Project description:Import of yeast peroxisomal matrix proteins is initiated by cytosolic receptors, which specifically recognize and bind the respective cargo proteins. At the peroxisomal membrane, the cargo-loaded receptor interacts with the membrane docking complex, composed of Pex14p, Pex17p and Pex13p. Previous data suggest that this interaction triggers the formation of an import pore for further translocation of the cargo. The mechanistic principles and the underlying mechanism are however unclear, mainly because structures of higher order assemblies are still lacking. Here, using an integrative approach, we provide the first structural characterization of the major components of the peroxisomal docking complex Pex14p/Pex17p, in a native bilayer environment and reveal its subunit organization. Our data show that three copies of Pex14p and a single copy of Pex17p assemble to form a 20 nm rod-like particle. The different subunits are arranged in a parallel manner, showing interactions along their complete sequences and providing receptor binding-sites on both membrane sides. The long rod facing the cytosol is mainly formed by the coiled-coil domains of Pex14p and Pex17p, possibly providing the necessary structural support for the formation of the import pore. Further implications of Pex14p/Pex17p for formation of the peroxisomal translocon are discussed.

2020-12-16 | PXD016304 | Pride

Phosphorylation of the receptor protein Pex5p modulates import of PTS1 cargoes into peroxisomesPhosphorylation of the receptor protein Pex5p modulates import of PTS1 cargoes into peroxisomes

Project description:Peroxisomes are dynamic organelles with vital functions in cellular metabolism and dysfunction of peroxisomes is associated with human diseases. To fulfill their multiple roles, peroxisomes rely on import of nuclear-encoded matrix proteins, most carrying a peroxisomal targeting signal (PTS) 1. The receptor Pex5p recruits PTS1-proteins for import into peroxisomes; whether and how this process is posttranslationally regulated is unknown. Here, we identify 22 phosphorylation sites of Pex5p. Yeast cells expressing phospho-mimicking Pex5p-S507/523D (Pex5p-2D) show a decreased peroxisomal import of GFP-SKL. We show that the binding affinity between PTS1-protein and Pex5p-2D is reduced. An in vivo analysis of the effect of the phosphomimicking mutants on all known PTS1-proteins revealed that import of most, but not all, cargo proteins is affected. The physiological effect of the phosphomimetic mutations correlate with the binding affinity of the corresponding extended PTS1-sequences. Thus, we report a novel Pex5p phosphorylation-dependent mechanism for regulating PTS1-protein import into peroxisomes.

2023-03-10 | PXD015676 | Pride

Identification of the PhoB regulon and role of PhoU in the phosphate-starvation response of Caulobacter crescentus (ChIP-seq)

Project description:An ability to sense and respond to changes in extracellular phosphate is critical to the survival of most bacteria. For Caulobacter crescentus, which typically lives in phosphate-limited environments, this process is especially crucial. Like many bacteria, Caulobacter responds to phosphate limitation through a conserved two-component signaling pathway called PhoR-PhoB, but the direct regulon of PhoB in this organism is unknown. Here, we use ChIP-Seq to map the global binding patterns of the phosphate-responsive transcriptional regulator PhoB in both phosphate-limited and -replete conditions. Combined with genome-wide expression profiling, our work demonstrates that PhoB is induced to regulate nearly 50 genes in phosphate-starved conditions. The PhoB regulon is comprised primarily of genes known or predicted to help Caulobacter scavenge for and import inorganic phosphate, including 15 different membrane transporters. We also investigated the regulatory role of PhoU, a widely conserved protein proposed to coordinate phosphate import with expression of the PhoB regulon by directly modulating the histidine kinase PhoR. However, our studies show that it likely does not play such a role in Caulobacter as depleting PhoU has no significant effect on PhoB-dependent gene expression. Instead, cells lacking PhoU exhibit a striking accumulation of large polyphosphate granules suggesting that PhoU participates in controlling intracellular phosphate metabolism. An allele of phoB bearing a C-terminal 3x-flag tag was integrated at its native locus, and ChIP followed by deep sequencing on Illumina MiSeq was performed on samples grown in rich medium, phosphate-limited medium, and in a pstS::Tn5 mutant background in rich medium.

2016-08-06 | E-GEOD-71860 | biostudies-arrayexpress

A genome-wide screen for peroxisome regulators connects peroxisomes with Wnt signaling through RNF146 and tankyrase

Project description:Peroxisomes are membrane-bound organelles that help cells specialize their metabolism. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. Thus, we performed a genome-wide CRISPRi screen to identify novel factors involved in peroxisomal homeostasis. We found that transcriptional inhibition of RNF146, an E3 ligase activated by poly(ADP-ribose), dramatically reduced the import of proteins into peroxisomes. The observed RNF146-mediated loss of peroxisome import depended on the stabilization and activity of the poly(ADP-ribose) polymerase tankyrase, which binds the peroxisomal membrane protein PEX14. We propose a model in which RNF146 and tankyrase regulate peroxisome import efficiency by tuning PARsylation of proteins at the peroxisome membrane. Interestingly, we found that perturbations to peroxisomes altered tankyrase’s selection of substrates, including the beta-catenin destruction complex component AXIN1. The loss of peroxisomes caused tankyrase and RNF146-dependent degradation of AXIN1 and a concomitant increase of beta-catenin transcription. Together, these observations not only suggest previously undescribed roles for RNF146 in peroxisomal regulation, but also a novel role in bridging peroxisome function with Wnt/beta-catenin signaling during development.

2024-06-01 | GSE266892 | GEO

A genome-wide screen for peroxisome regulators connects peroxisomes with Wnt signaling through RNF146 and tankyrase [Amplicon-sequencing]

2024-06-01 | GSE266855 | GEO

Genome-wide maps of chromatin states during B-cell to Macrophage lineage switching

Project description:Using homogenous populations of cells undergoing lineage switching we studied enhancer nucleation. Examination of 3 histone marks several time points after induction of transdifferentiation

2015-07-29 | E-GEOD-53173 | 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