EMBO/sd-character-level-ner huggingface dataset:
Comprehensive substrate screening on protein microarrays (protoarray®) identifies 161 candidate substrates of SCFFbxw5 A.Figure 1A. Coomassie-stained SDS-polyacrylamide gel electrophoresis (PAGE) of different proteins used in the assay. Cul1 was obtained using a split and co-express system (in which the C- and N-terminal domains are co-expressed as individual proteins and therefore run as two distinct bands at around 50 kDa) followed by in vitro neddylation. SCFFbxw5 complexes were prepared by mixing equimolar amounts of Fbxw5/Skp1 and Cul1~Nedd8/Rbx1 sub-complexes. Numbers left of the gel indicate molecular weight marker in kilo-Dalton (kDa, same accounts for all following gels and blots). B. Workflow and example of a sub-array of the protoarray screen. Protein microarrays containing more than 9000 human proteins spotted in duplicates were incubated with 15 µM FITC-labelled ubiquitin (Ub), 100 nM E1 (Uba1-His6), E2s (0.5 µM each of UbcH5b and Cdc34) and 0.15 µM SCFFbxw5 for 1.5 hours at 37°C. Right panel shows overlay of a selected sub-array probed with (red) or without (green) SCFFbxw5 complexes. White box marks the established substrate Sas6. C. Comparison of protoarray signal intensities of candidate substrates probed with or without SCFFbxw5 complexes. Sas6, Sec23b and MCAK are marked as red dots (other published substrates (e.g. Ask1, Eps8) were not among the 9000 proteins spotted on the array). Note that axes have different scaling. D. Cellular components GO analysis of identified substrates using DAVID webtool with protoarray proteins as background. E. Validation of individual targets by manually curated in vitro ubiquitylation experiments. HA-tagged (hemagglutinin) candidate proteins were purified from Hek293T cells via anti-HA immunoprecipitation (IP) followed by HA-peptide elution. Candidates were incubated with 20 µM His6-Ubiquitin, 170 nM E1, E2s (0.5 µM each of UbcH5b and Cdc34) and 5 mM ATP in the presence or absence of 0.1 µM SCFFbxw5 for 2 hours at 37°C. Substrates were detected via SDS-PAGE followed by western blotting using anti-HA antibodies for detection.
Figure 1Activated GFAP+ astrocytes in white matter MS lesions with inflammatory infiltrates and demyelination show an upregulation of OTUB1 (arrows). Photomicrographs are obtained from case 9 (A) and case 5 (B) listed in Table EV1. Data are representative for all 10 MS patients analyzed. Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-GFAP (FITC); original magnification ×400; scale bars correspond to 50 µm.
Fig.Figure 2Representative Giemsa staining of sorted ATM subsets (MHCIIlow, MHCIIhi, and CD11c+) from obese (HFD 16 weeks) eWAT. Scale bar, 10 μm. Quantification of intracellular vacuole sizes in the three different ATM subsets (n = 4 mice). The average size is presented as mean ± SD. Statistical significance was determined using one-way ANOVA test. **P < 0.01, ****P < 0.0001. Representative confocal 3D images of LysoTracker (red), DAPI (blue), and BODIPY (green) stained ATM subsets obtained from eWAT of HFD (16 weeks) treated mice (n = 8 mice from two independent experiments). The merged figures are the result of the overlap of all three fluorochromes. Scale bar, 10 μm. Representative histograms showing the mean fluorescence intensity of BODIPY-stained ATM subsets obtained from obese (HFD 16 weeks) eWAT (n = 4 mice). Heatmap showing fatty acid lipolysis- and uptake-related genes differentially expressed among the eWAT ATM subsets from HFD (16 weeks) treated mice. Each cluster has three biological replicates. The z-score of the gene expression profiles gives a scale to measure the differential expression. Gene set enrichment analysis (GSEA) identified significant transcriptional upregulation in oxidative phosphorylation and the TCA cycle/respiratory electron transport signaling pathway in CD11c+ ATMs when compared with MHCIIhi ATMs obtained from eWAT of HFD-treated (HFD 16 weeks) mice. Gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) with false discovery rate (FDR) <0.05. qPCR validation of Lpl and Fabp4 expression in sorted ATM subsets from eWAT of ND- and HFD-treated (16 weeks) mice (n = 3 of 5 pooled mice each). Data are presented as mean ± SD. *P < 0.05; **P < 0.01, ***P < 0.001; ****P < 0.0001; ns: no significant difference. Representative FACS analysis of CD36 expression in ATM subsets from eWAT of HFD (16 weeks) mice (n = 4 mice). Mito Stress assay of sorted ATM subsets (red, MHCIIlow; green, MHCIIhi; and blue, CD11c+) from 16-week-HFD obese mice showing overall oxygen consumption rate (OCR), maximal respiration, spare capacity respiration, basal respiration, ATP production, and non-mitochondrial respiration. OCR data shown are representative of four independent experiments and expressed as mean ± SD (n= 4 MHCIIlow; n= 7 MHCIIhi; n=5 CD11c+), with statistical significance determined using one-way ANOVA test (*P < 0.05; **P < 0.01; ***P < 0.001; ns: no significant difference).
Early exposure to CX546 rescues selected morphological and transcriptional defects of null neurons A: Schematic representation of the CX546 treatment.Figure 3A: Schematic representation of the CX546 treatment. The drug was added to the cell medium from DIV3 to DIV6 (early) and from DIV7 to DIV10 (late); a complete wash-out of the medium was performed at the end of each treatment (DIV7 and DIV11 respectively). B,C: Five morphological parameters were measured in untreated and treated null neurons at DIV14. One-way ANOVA indicated a significant treatment effect for the maximal dendritic length (F=6,306;p=0,0039), total dendritic length (F=4,880;p=0,0126), number of intersections (F=10,70; p=0,0003) and soma area (F=7,721;p=0,0015). Tukey's multiple comparison test was used to assess differences between null neurons and early and late treated neurons. *: p-value<0.05; **: p-value<0.01; ***: p-value<0.001. The variation of each of the selected parameters is summarized in the radar plot (C). Sample size (panels B,C): n≥18 wells for ctrl group and n≥10 wells for the treatment groups deriving from three independent preparations; for each well we measured at least 15 cells. Each point is representative of a single well. Values are represented as mean ± SEM. The three PCA analyses are based on the 43 genes selected in Appendix Figure S2 and highlight the transcriptional differences between wt (in blue), ko (in red) and ko CX546 treated (light and dark green for early and late treatment respectively) samples. Bar graphs represent the expression values (mean ± SEM) of 27 genes, selected for their downregulation in null samples at DIV 14 (p-value <0,07; see Appendix Figure S2), after CX546 administration in the two different time windows (early in G and late in H). One-way ANOVA followed by Dunnett's multiple comparison test was used to compare the expression of each gene between Mecp2 null early and late treated samples and their corresponding untreated controls (set to 1, red dotted line). *: p-value<0.05; **: p-value<0.01, ***: p-value<0.001, ****: p-value<0.0001. Sample size: n≥8 wells deriving from two independent preparations. Each point is representative of a single well.
Evaluation of protein degradation and synthesis pathways.Figure 2A. Western blot of quadriceps muscle from summer active (S) and hibernating (H) squirrels using antibodies against the proteins indicated. An increased abundance of P−Foxo3a (serine−253) is accompanied by a decrease in P−Akt (serine−478). Corresponding densitometry of P−Akt and P−Foxo3a as a function of total Akt and Foxo3a. B. Relative mRNA levels for four Foxo3a downstream targets show no significant changes during hibernation. C. Western blots analysis of mTOR downstream targets shows significant upregulation of P−P70 and P−4E−BP1 during hibernation.
Figure 2A - Cell-specific deletion of ChAT was achieved by crossing ChATfl/fl mice with LysM-Cre (MΦ), Cd4-Cre (T cells) or Mb1-Cre (B cells) mice. B - ChAT deletion was confirmed in MΦ, CD4+ and CD8+ T cells, and B cells sorted from IWAT of ChATfl/fl;LysM-Cre (n = 3), ChATfl/fl;Cd4-Cre (n = 4 for ChATfl/fl, n = 3 for Cre for CD4, n = 4 for CD8) and ChATfl/fl;Mb1-Cre mice (n = 5 for ChATfl/fl and n = 6 for Cre) respectively. Body weight (C) of ChATfl/fl;LysM-Cre (n = 7 for ChATfl/fl, n = 8 for Cre ChATfl/fl;Cd4-Cre (n = 6 for ChATfl/fl and n = 7 for Cre ChATfl/fl;Mb1-Cre (n = 12 in C, n = 9 for ChATfl/fl, n = 8 for Cre and littermate ChATfl/fl mice housed at RT. IWAT weight (D) of ChATfl/fl;LysM-Cre (n = 7 for ChATfl/fl, n = 8 for Cre , ChATfl/fl;Cd4-Cre (n = 6 for ChATfl/fl and n = 7 for Cre in ChATfl/fl;Mb1-Cre n = 9 for ChATfl/fl, n = 8 for Cre and littermate ChATfl/fl mice housed at RT. E-G - mRNA expression of Chrna2 and thermogenic genes in IWAT of ChATfl/fl;LysM-Cre (n = 24 for ChATfl/fl_RT, n = 25 for Cre_RT, n = 20 for ChATfl/fl_CE, n = 20 for Cre_CE) (E), ChATfl/fl;Cd4-Cre (n = 17 for ChATfl/fl_RT, n = 22-23 for Cre_RT, n = 19 for ChATfl/fl_CE, n = 22 for Cre_CE) (F), ChATfl/fl;Mb1-Cre (n = 10 for ChATfl/fl_RT, n = 11 for Cre_RT, n = 9-12 for ChATfl/fl_CE, n = 13 for Cre_CE) (G) and littermate ChATfl/fl mice housed at RT or 4oC (CE) for 6 h. An insert graph in (E) highlights mRNA expression of Chrna2 and thermogenic genes in IWAT of ChATfl/fl and ChATfl/fl;LysM-Cre mice after 6 h CE. H - LC/MS-MS was used to quantify Ach secretion from IWAT SVF cells isolated from ChATfl/fl and ChATfl/fl;LysM-Cre mice housed at RT or 4 h CE (n = 3). n.s.: not significant. I - Immunoblotting for UCP1 and GAPDH (loading control) in IWAT from ChATfl/fl (n = 7) and ChATfl/fl;LysM-Cre (n = 5) mice after 6 h CE. BAT served as a positive control (PC) for UCP1 expression. Film was subjected to a short and long exposure and size (kDa) is marked on the right hand side. #: non-specific bands. J - Basal and oligomycin-insensitive OCR of IWAT from cold-exposed ChATfl/fl (n = 11) and ChATfl/fl;LysM-Cre (n = 13) mice for 6 h. K - Average whole-body oxygen consumption rate (OCR) of ChATfl/fl (n = 10) and ChATfl/fl;LysM-Cre (n = 14) mice housed in metabolic chambers at RT or CE for 6 h (from 9 a.m. to 3 p.m.). L - Relative mRNA expression of Chrna2 and thermogenic genes in BAT of ChATfl/fl and ChATfl/fl;LysM-Cre mice housed at RT or 6 h CE (n = 12 for ChATfl/fl_RT, n = 13 for ChATfl/fl;LysM-Cre_RT, n = 15 for ChATfl/fl_CE, n = 14 for ChATfl/fl;LysM-Cre_CE).
+/- preneoplastic tissue versus tumors A Reclustered EPCAM-negative cells (excluding clusters 1, 6, 9 and 10 from E) revealed immune/stromal cells in the microenvironment, identified using lineage markers.Figure 5A Reclustered EPCAM-negative cells (excluding clusters 1, 6, 9 and 10 revealed immune/stromal cells in the microenvironment, identified using lineage markers. B Combined t-SNE plot as in (A) of the single-cell transcriptomes of immune and stromal cells from preneoplastic tissue of BRCA1 mutation carriers (blue; preneo) and BRCA1-associated TNBCs (yellow; tumor). C t-SNE plots showing expression profiles of cardinal markers of immune and stromal cells. D Bar plots showing the percentage of cells expressing typical immune cell (including Treg) genes for clusters in (A) by preneoplastic vs tumor. E Left panel, same t-SNE map as in (A) but separated into cells from preneoplastic (blue) and tumor specimens (yellow). Endothelial cell (endo), fibroblast cell (fibro) and pericytes (peri) clusters are marked. Right panel, proportion of clusters as in (A) according to tissue type. F Relative cluster sizes as in (E) but by individual patient. G Co-immunofluorescence of tissue stained for the epithelial marker (cytokeratin 19; yellow) and the tumor-associated macrophage marker CX3CR1 (magenta). DAPI is shown in white (n=2 preneoplastic samples; n=2 tumors). Scale bar, 100 μm. H Heat map of top differentially expressed genes in the major immune/stromal cell clusters, identified in (A). BRCA1+/- preneoplastic cells, blue; BRCA1-associated tumor cells, yellow.
Dcp-1 is required for nutrient starvation–induced germarium cell death, and the IAP protein Bruce inhibits germarium and mid-oogenesis cell death.Figure 6.(A) Ovaries were stained with TUNEL (green) to detect DNA fragmentation. Clusters of cysts with TUNEL staining were observed in region 2 in nutrient-deprived w1118 files. In Dcp-1Prev flies, fewer TUNEL-positive cysts in region 2 were observed. Under well-fed conditions, numerous TUNEL-positive cysts were observed in BruceE81 flies. DAPI staining of nuclei is shown in white. (B) Numerous degenerating stage 8 egg chambers (arrows) with Bruce-positive staining (green) were observed in well-fed BruceE81 flies. DAPI staining of nuclei (white) is shown on the right.
Figure 3Isolated cryo-EM density of SecYEG with the fitted molecular model of the translocon in front and the cytoplasmic views. SecY is displayed in rainbow pattern, SecE in purple, and SecG in green. Dashed box: A contact site between tilted SecE TMHs 1/2 and SecY TMH 8. Cryo-EM density corresponding to the ribosomal RNA helix 59 ("H59") is displaced toward the nanodisc. No contact with the lipid bilayer could be detected. Blue ribbon: Structure of the translocon-free 50S ribosomal subunit (PDB ID: 4UY8). Central cross-section through the SecYEG model. The "plug" TMH 2a occupies the central position, thus keeping the translocon sealed. The nanodisc perimeter is indicated as a dashed circle. The lateral gate of nanodisc-embedded translocon undergoes rearrangements relatively to a quiescent conformation (left, PDB ID 5AWW) and an RNC-bound detergent-solubilized state (right, PDB ID 5GAE).
Figure 7(A) Discrepancies between the result of the flow cytometry test and previous PCR or ELISA tests within the CBMSO cohort. (B) A neutralization assay with S protein-pseudotyped lentivirus was carried out to resolve the discrepancies. Data represent the mean±SD of duplicates. *, p<0.05; **, p<0.005; ***, p<0.0005; *****, p<0.000005 (Paired two-tailed t-test comparing all serum dilutions to the pre-COVID sample). (C) Classification of the CBMSO cohort according to the Score generated from S/EGFR data. The Broken line indicates the 0.024 threshold above which samples are considered positive.
Figure 3RNA classes are labeled on the outer ring (rRNA has been omitted to clarify interactions between other RNA classes). RNA-RNA interactions with more than two unique hybrid sequences are presented. The thickness of the link represents the number of unique hybrid sequences recovered (up to a maximum of 50 sequences). RNA-RNA interactions where both hybrid halves overlap an Hfq binding site are colored blue and non-overlapping interactions are colored green.
Fig.Figure 2A, Parental HEK293T, HET and HOM1 cells were treated with Activin A or Activin B for the indicated times. Quantifications are shown on the right. Data information: quantifications are the average normalized intensities ± SEM of between 3 and 10 In A, quantifications are the levels of pSMAD1/5 normalized to Actin ns, not significant; *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. The p-values are from two-way ANOVA with Dunnett's post-hoc test. In all panels, Western blots of whole cell lysates were probed with the antibodies indicated. , B. Parental HEK293T, HET and HOM1 cells were treated with BMP2 for the indicated times. Quantifications are shown on the right. Data information: quantifications are the average normalized intensities ± SEM of independent experiments in B , the quantifications are expressed as fold changes relative to 1 h of ligand stimulation. ns, not significant; *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. The p-values are from two-way ANOVA with Dunnett's post-hoc test. In all panels, Western blots of whole cell lysates were probed with the antibodies indicated. C. Parental HEK293T, S2/3 dKO1, S6/7 dKO1 and S6/7 dKO2 cells were treated with Activin A for the indicated times. Data information: quantifications are the average normalized intensities ± SEM of between 3 and 10 in C, the quantifications are expressed as fold changes relative to 1 h of ligand stimulation. ns, not significant; *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. The p-values are from two-way ANOVA with Dunnett's post-hoc test. In all panels, Western blots of whole cell lysates were probed with the antibodies indicated. D. Parental HEK293T, S2/3 dKO1 and HOM1 cells were treated with Activin A for the indicated times. Data information: ns, not significant; *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. The p-values are from two-way ANOVA with Dunnett's post-hoc test. In D quantifications are from a representative experiment and are the intensities of pSMAD1/5 normalized to Actin, expressed as fold change relative to untreated cells for each clone. In all panels, Western blots of whole cell lysates were probed with the antibodies indicated.
a) Ultrastructural evidence of autophagy induced by depletion of p53 with a specific siRNA or pharmacological inhibition of p53 with PFT-α in HCT116 cells.figf1(a) Ultrastructural evidence of autophagy induced by depletion of p53 with a specific siRNA or pharmacological inhibition of p53 with PFT-α in HCT116 cells. (b) Autophagy induced by PFT-α, p53 knockdown, or p53 knockout in HCT116 cells. The number of autophagosomes and autolysosomes was determined for at least 50 cells in 3 independent experiments (mean ± s.e.m.; *P 0.05). Culture in nutrient-free (NF) conditions was used as a positive control. (c) Effect of p53 on the maturation of LC3. Immunoblots are shown for wild-type (WT) or p53−/− HCT116 (n = 3). (d) GFP-LC3 puncta induced by PFT-α, p53 knockdown or knockout. WT and p53−/− HCT116 cells were transfected with control or p53-specific siRNAs, re-transfected with a GFP-LC3 plasmid, cultured in complete medium for 24 h and kept for 6 h in the presence or absence of 30 μM PFT-α. The percentage of cells showing accumulation of GFP-LC3 in puncta (GFP-LC3vac) is reported (mean ± s.d., n = 3; *P 0.05). (e) GFP-LC3 puncta in p53−/− MEF, compared with WT MEF transfected with GFP-LC3 (mean ± s.d., n = 3; *P 0.05). (f) GFP-LC3 dots in tissues from p53+/+ or p53−/− mice expressing a GFP-LC3 transgene (mean ± s.d.; *P 0.05), without or after 24 h of starvation. The number of GFP-LC3 dots per area was determined for a minimum of 4 fields (at ×400 magnification for 4 slides per animal, 3 animals per condition). (g) TEM pictures of p53−/− and p53+/− mouse livers. p53−/− hepatocytes carry approximately 3 autophagosomes, p53+/− controls approximately 1 per cell. (h) Modulation of DsRed::LGG-1 levels by the p53 orthologue CEP-1 in C. elegans. Representative pictures are shown for WT animals and for nematodes carrying a cep-1 deletion allele (gk138). The count of puncta per cell was 6.9 ± 3.3 for WT, 52.2 ± 9.4 for cep-1 (gk138) embryos (mean ± s.e.m. for 20 individuals, 5 cells per embryo). The quantification of DsRed::LGG-1 puncta is shown for the indicated genetic backgrounds and conditions (dots represent pixel intensity for individual embryos).
Figure 4A Overlap between the 488 FXR2P targets and epilepsy risk genes (75 of 1'089; Fisher's exact test, p < 0.001). B String database was used to classify FXR2P and epilepsy risk genes that are part of one network. C Validation of RIP-seq by RT-qPCR. Shown are the correlation of the enrichment observed in log2 RIP-seq (X-axis) and log2 RT-qPCR (Y-axis) for 8 epilepsy-relevant FXR2P targets (red) and 8 FXR2P non-targets (black). Each point represents an individual mRNA, quantified using both methods (r = 0.8551, *** p < 0.001, R2 = 0.712). mRNAs are normalized for the average of all the 16 mRNAs.
Figure 3Top, representative western blot data of HDAC1 and TDP-43 in extracts obtained following RIPA fractional extraction in the frontal cortices and hippocampus from 6-mon-old of FTLD-TDP or WT mice. Bottom, semi-quantification of HDAC1 and TDP-43 expression levels. N = 5 mice per group, data are presented as mean ± SEM (%), **** p < 0.0001 by multiple t-tests. Top, representative western blot data of HDAC1 and TDP-43 in the cytosolic and nuclear extracts. Bottom, quantification of HDAC1 and TDP-43 levels. N = 5 mice per group, data are presented as mean ± SEM (%), *** p = 0.0005 (TDP-43) or 0.0004 (HDAC1); **** p < 0.0001 by multiple t-tests. IF staining of HDAC1 and SMI-32 in the regions of frontal cortices from WT and FTLD-TDP Tg mice. Scale bar: 150 μm. Blocked area in left bottom picture is showed in a magnified view in the right bottom picture. Scale bar: 50 μm. Nuclear HDAC1 activity assay from frontal cortices and hippocampus in 6-mon-old of FTLD-TDP and WT mice. TSA: nuclear extracts that were treated with Trichostatin A (TSA, an HDAC inhibitor) as a negative control for HDAC1-transferred fluorescent activity during the HDAC1 activity assay. N = 5 mice per group, data are presented as mean ± SEM (%), *p = 0.0415 by t-test. Left, representative western blot data of nuclear acetylated-histone H3 (Lys 9/14) and total-histone H3 in 6-mon-old of WT and FTLD-TDP Tg mice. Right, quantification of nuclear acetylated-histone H3/total-histone H3 ratio. N = 5 mice per group, data are presented as mean ± SEM (%), * p = 0.0147 by t-test.
Figure 7(A) The response of a mitochondrial matrix-localized Grx1-roGFP2 probe to 1 mM H2O2. in BY4742 wild-type cells with an empty vector, in Δglr1 cells transformed either with an empty vector or a vector encoding wild-type Glr1 or the cytosolic form of Glr1, where the MTS-encoding region was removed, or in Δglr1Δprx1 cells transformed either with an empty vector or a vector encoding the cytosolic form of Glr1. Cells were grown to exponential phase in SGal (-Leu, -Ura) medium. Error bars represent the standard deviation (n = 3 biological replicates, with cells obtained from 3 independent cultures for every strain and probe combinations. For each biological replicate three technical replicates were performed). (B) Growth curve of wild-type, Δprx1, Δglr1 and Δglr1Δprx1 cells in SD medium complemented with all amino acids (n = 3 biological replicates). Significance for the difference in the time the cultures reach 50% of their maximal OD600 was assessed with the t-test. Error bars (as ribbon) represent the standard deviation (n = 4 biological replicates, with cells taken from independent cultures for each individual biological replicate). (C) H2O2 'acute stress' assay. Wild-type, Δprx1, Δglr1 and Δglr1Δprx1 cells pre-grown in SGal medium complemented with all amino acids to early exponential phase. Cells were treated with H2O2 at the indicated concentrations for 30 mins. Subsequently cells were diluted, and a fixed volume plated on YPD plates. The number of viable colonies was counted after 2 days growth at 30°C, here represented as a percentage relative to the 0 mM pre-treatment. Error bars represent standard deviation (n = 3 biological replicates, with cells taken from independent cultures for each individual biological replicate). An inset with a different scale on the y-axis is presented for the 1 and 5 mM concentration to allow better interpretation. (D) H2O2 'acute stress' assay. Δprx1Δglr1 cells co-transformed with an empty plasmid or with a plasmid encoding either wild-type Prx1, the P233stop or the C91A variants were grown in SGal (-Ura) medium to early exponential phase. Cells were treated with the indicated amounts of H2O2 for 30 mins. Subsequently, the cells were diluted, and a fixed volume plated on YPD plates. The number of viable colonies was counted after 2 days growth at 30°C, here represented as a percentage relative to the 0 mM treatment. Error bars represent standard deviation (n = 3 biological replicates, with cells taken from independent cultures for each individual biological replicate). (E) Model. Prx1 drives oxidation of glutathione upon exposure to hydrogen peroxide. During acute H2O2 stress, Prx1 becomes hyperoxidized, which effectively uncouples the glutathione pool from H2O2. Prx1 hyperoxidation thus helps to limit GSSG accumulation and contributes to cell survival.