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PubMed2003

Pseudorabies virus US3 protein kinase mediates actin stress fiber breakdown.

Disruption of specific components of the host cytoskeleton has been reported for several viruses and is thought to be beneficial for viral replication and spread. Our previous work demonstrated that infection of swine kidney (SK-6) cells with pseudorabies virus (PRV), a swine alphaherpesvirus, induced actin stress fiber breakdown. In the present study, using several PRV deletion mutants, we found that the US3 serine/threonine (S/T) protein kinase is involved in breakdown of actin stress fibers in different PRV-infected cell lines. Further, by transfection assays, we showed that PRV US3 itself, in the absence of other viral proteins, is able to trigger actin stress fiber breakdown when it is localized in sufficient amounts in the nucleus.

Actins↗
PubMed2006

Proteomic analysis of acidic chaperones, and stress proteins in extreme halophile Halobacterium NRC-1: a comparative proteomic approach to study heat shock response.

BACKGROUND: Halobacterium sp. NRC-1 is an extremely halophilic archaeon and has adapted to optimal growth under conditions of extremely high salinity. Its proteome is highly acidic with a median pI of 4.9, a unique characteristic which helps the organism to adapt high saline environment. In the natural growth environment, Halobacterium NRC-1 encounters a number of stressful conditions including high temperature and intense solar radiation, oxidative and cold stress. Heat shock proteins and chaperones play indispensable roles in an organism's survival under many stress conditions. The aim of this study was to develop an improved method of 2-D gel electrophoresis with enhanced resolution of the acidic proteome, and to identify proteins with diverse cellular functions using in-gel digestion and LC-MS/MS and MALDI-TOF approach. RESULTS: A modified 2-D gel electrophoretic procedure, employing IPG strips in the range of pH 3-6, enabled improved separation of acidic proteins relative to previous techniques. Combining experimental data from 2-D gel electrophoresis with available genomic information, allowed the identification of at least 30 cellular proteins involved in many cellular functions: stress response and protein folding (CctB, PpiA, DpsA, and MsrA), DNA replication and repair (DNA polymerase A alpha subunit, Orc4/CDC6, and UvrC), transcriptional regulation (Trh5 and ElfA), translation (ribosomal proteins Rps27ae and Rphs6 of the 30 S ribosomal subunit; Rpl31eand Rpl18e of the 50 S ribosomal subunit), transport (YufN), chemotaxis (CheC2), and housekeeping (ThiC, ThiD, FumC, ImD2, GapB, TpiA, and PurE). In addition, four gene products with undetermined function were also identified: Vng1807H, Vng0683C, Vng1300H, and Vng6254. To study the heat shock response of Halobacterium NRC-1, growth conditions for heat shock were determined and the proteomic profiles under normal (42 degrees C), and heat shock (49 degrees C) conditions, were compared. Using a differential proteomic approach in combination with available genomic information, bioinformatic analysis revealed five putative heat shock proteins that were upregulated in cells subjected to heat stress at 49 degrees C, namely DnaJ, GrpE, sHsp-1, Hsp-5 and sHsp-2. CONCLUSION: The modified 2-D gel electrophoresis markedly enhanced the resolution of the extremely acidic proteome of Halobacterium NRC-1. Constitutive expression of stress proteins and chaperones help the organism to adapt and survive under extreme salinity and other stress conditions. The upregulated expression pattern of putative chaperones DnaJ, GrpE, sHsp-1, Hsp-5 and sHsp-2 under elevated temperature clearly suggests that Halobacterium NRC-1 has a sophisticated defense mechanism to survive in extreme environments.

Journal Article↗
PubMed2003

Hepatitis C virus in the human liver transplantation model.

Hepatitis C virus-related liver failure is the single leading indication for liver transplantation, and the study of HCV in the transplant setting has enhanced the understanding of the natural history of disease and putative mechanisms by which HCV causes liver injury. In a subset of patients, allograft cirrhosis develops within a few years after transplantation, and recent findings suggest these individuals are immunologically impaired compared with individuals with mild HCV recurrence at long-term follow-up. Fig. 9 shows a conceptual paradigm of mechanisms potentially involved in shaping HCV outcome after transplantation. It is possible that relative antiviral control by innate and adaptive immune responses (to maintain HCV replication below a certain threshold) prevents direct cytopathic injury and induction of oxidative stress and apoptosis of cells. Additional phenomena that may contribute to induction of apoptosis (eg, genetic polymorphisms within the donor organ. CMV coinfection, and ischemic-preservation injury) may augment the initial cascade of liver injury. Recruitment to the allograft of nonspecific cells may decrease viral replication by way of noncytolytic mechanisms or augment viral replication (eg, Th2 phenotype) and direct cytopathic injury. The immune response is likely insufficiently vigorous to keep viral replication under control, but may maintain chronic liver injury. The liver transplant model is unique in that distinct phenotypic outcomes can be observed over a short period of time. A consideration of the temporal evolution of different mechanisms is also important, because mechanisms that initially predominate may become less important over time, and conversely, as suggested with the inverse correlation between viral load at 5 years and allograft fibrosis, new immune responses may emerge that modify the host-virus interaction. Prospective characterization of the immunoregulatory and virologic mechanisms involved in the liver transplantation model hopefully will help unravel the causal basis of reported associations, lead to the development of highly specific therapeutic strategies, and ultimately diminish the rate of graft loss from recurrent disease.

Animals↗
PubMed2004

Nitric oxide as an endogenous mutagen for Sendai virus without antiviral activity.

Nitric oxide (NO) may affect the genomes of various pathogens, and this mutagenesis is of particular interest for viral pathogenesis and evolution. Here, we investigated the effect of NO on viral replication and mutation. Exogenous or endogenous NO had no apparent antiviral effect on influenza A virus and Sendai virus. The mutagenic potential of NO was analyzed with Sendai virus fused to a green fluorescent protein (GFP) gene (GFP-SeV). GFP-SeV was cultured in SW480 cells transfected with a vector expressing inducible NO synthase (iNOS). The mutation frequency of GFP-SeV was examined by measuring loss of GFP fluorescence of the viral plaques. GFP-SeV mutation frequency in iNOS-SW480 cells was much higher than that in parent SW480 cells and was reduced to the level of mutation frequency in the parent cells by treatment with an NO synthase (NOS) inhibitor. Immunocytochemistry showed generation of more 8-nitroguanosine in iNOS-SW480 cells than in SW480 cells without iNOS transfection. Authentic 8-nitroguanosine added exogenously to GFP-SeV-infected CV-1 cells increased the viral mutation frequency. Profiles of the GFP gene mutations induced by 8-nitroguanosine appeared to resemble those of mutations occurring in mouse lungs in vivo. A base substitution that was characteristic of both mutants (those induced by 8-nitroguanosine and those occurring in vivo) was a C-to-U transition. NO-dependent oxidative stress in iNOS-SW480 cells was also evident. Together, the results indicate unambiguously that NO has mutagenic potential for RNA viruses such as Sendai virus without affecting viral replication, possibly via 8-nitroguanosine formation and cellular oxidative stress.

Animals↗
PubMed2000

Characterization of heat, oxidative, and acid stress responses in Brucella melitensis.

Brucella melitensis is a facultative intracellular pathogen which is able to survive and replicate within phagocytic cells. Therefore, it has to adapt to a range of different hostile environments. In order to understand the mechanisms of intracellular survival employed by virulent B. melitensis 16M, an initial approach consisting of analysis of the differences in patterns of protein synthesis in response to heat, oxidative, and acid pH stresses by two-dimensional (2-D) polyacrylamide gel electrophoresis was used. Depending on the stress, this involved about 6.4 to 12% of the 676 protein spots detected in 2-D gel electrophoresis. On the basis of N-terminal sequence analysis and database searching, 19 proteins whose level of synthesis was up- or down-regulated by stress conditions were identified. Some of them were previously reported for Brucella, such as BvrR, DnaK, GroEL, and Cu-Zn superoxide dismutase (SOD). Eight other proteins closely matched proteins found in other bacteria: AapJ, alpha-ETF, ClpP, Fe and/or Mn SOD, malate dehydrogenase, IalB, 30S ribosomal protein S1, and pyruvate dehydrogenase E1 component beta subunit. Results indicated that B. melitensis could bring specific regulatory mechanisms into play in response to stress conditions. For example, the ribosome releasing factor in B. melitensis appeared to be a heat shock protein, whereas the ClpP protein, described as a heat shock protein for Escherichia coli, was strongly down-regulated in B. melitensis in response to heat stress. Some of the identified proteins and their potential specific regulation could be required for the adaptation of B. melitensis to environmental stresses encountered in phagocytic cells and possibly for bacterial virulence.

Acids↗
PubMed2000

Comparison of low-molecular-weight heat stress proteins encoded on plasmids in different strains of Streptococcus thermophilus.

Streptococcus thermophilus is used extensively for industrial fermentation of dairy products. Some strains of S. thermophilus are known to carry plasmids, and many of these plasmids are suspected of encoding low-molecular-weight heat stress proteins (Hsps) that may aid in survival under stressful conditions. In order to confirm the presence and examine the similarity of these low-molecular-weight Hsps, genes were identified and sequenced encoding Hsps on plasmids pER16 (4.5 kb), pER35 (10 kb), and pER36 (3.7 kb) from three different strains of S. thermophilus. The plasmid replication proteins were also sequenced to examine their relatedness. Amino acid sequence comparisons of the Hsps and of the replication proteins revealed a high degree of identity suggesting a common origin. Heat stress proteins enhance the viability of bacteria in extreme environments, and the presence of an Hsp encoded on a plasmid may enhance survival of S. thermophilus under harsh production conditions.

Amino Acid Sequence↗
PubMed1996

Adolescent stress alters ethanol ingestion and agonistic behavior in the male golden hamster.

These data suggest that shock stress during adolescence increases ETOH consumption and may contribute to an increase in aggression in early adulthood. Interestingly, shock stress without ETOH results in timid behavior in early adulthood. One might speculate that adolescent hamsters "self-medicate" to deal with continuous stress. However, because of the variability between experimental groups, it is necessary to replicate these studies with larger numbers of animals and expand the findings to include blood ETOH concentrations.

Age Factors↗
PubMed2026

The TUBG meshwork is associated with centromere dynamics and micronuclear organization.

This study investigates how γ-tubulin and the centrosome contribute to interphase centromere dynamics and nuclear organization. Although classically associated with mitotic microtubule nucleation, here we show that γ-tubulin associates with chromatin and is enriched within centromere-defined volumes. Using live-cell imaging, immunofluorescence, and chromatin immunoprecipitation sequencing, we detect γ-tubulin-associated signal at satellite-rich, centromere-proximal chromatin. Reduced γ-tubulin levels are associated with increased centromere fluorescence intensity and reduced mobility, linking the γ-tubulin network to centromere organization. Under acute cisplatin-induced stress, centromere mobility increases, whereas centromere clustering is observed in separate fixed-cell analyses. Ser131 phosphorylation is associated with γ-tubulin self-assembly and centromere-related dynamics. Additionally, γ-tubulin accumulates in micronuclei, coinciding with increased replication-associated signal and DNA fluorescence. In primary clear cell renal cell carcinoma cells, stress is associated with higher γ-tubulin fluorescence intensity within centromere-defined volumes. Together, these findings support an association between the γ-tubulin meshwork and centromere organization, chromatin compartmentalization, and responses to genomic stress.

Centromere↗
PubMed2005

The plasmids of Chlamydia trachomatis and Chlamydophila pneumoniae (N16): accurate determination of copy number and the paradoxical effect of plasmid-curing agents.

A 7.5 kbp cryptic plasmid is found in almost all isolates of Chlamydia trachomatis. Real-time PCR assays, using TaqMan chemistry, were set up to quantify accurately both the chlamydial plasmid and the single copy, chromosomal omcB gene in the infectious, elementary bodies (EBs) of C. trachomatis L1 440. Plasmid copy number was also determined in the EBs of six other lymphogranuloma venereum (LGV) isolates (serovars L1-L3), ten trachoma isolates (serovars A-C) and nine urogenital isolates (serovars D-J). The results indicated an average plasmid copy number of 4.0+/-0.8 (mean+/-95 % confidence interval) plasmids per chromosome. During the chlamydial developmental cycle, up to 7.6 plasmids per chromosome were detected, indicating an increased plasmid copy number in the actively replicating reticulate bodies. Attempts to eliminate the plasmid from strain L1 440 using the plasmid-curing agents ethidium bromide, acridine orange or imipramine/novobiocin led to a paradoxical increase in plasmid copy number. It is speculated that the stress induced by chemical curing agents may stimulate the activity of plasmid-encoded replication (Rep) proteins. In contrast to C. trachomatis, only a single isolate of Chlamydophila pneumoniae bears a plasmid. C. pneumoniae strain N16 supports a 7.4 kbp plasmid in which ORF1, encoding one of the putative Rep proteins, is disrupted by a deletion and split into two smaller ORFs. Similar assay techniques revealed 1.3+/-0.2 plasmids per chromosome (mean+/-95 % confidence interval) in EBs of this strain. These findings are in agreement with the hypothesis that the ORF1-encoded protein is involved in, but not essential for, plasmid replication and control of copy number.

Acridine Orange↗
PubMed2004

Oxidative damage to specific proteins in replicative and chronological-aged Saccharomyces cerevisiae: common targets and prevention by calorie restriction.

Oxidative modifications of cellular components have been described as one of the main contributions to aged phenotype. In Saccharomyces cerevisiae, two distinct life spans can be considered, replicative and chronological. The relationship between both aging models is still not clear despite suggestions that these phenomena may be related. In this work, we show that replicative and chronological-aged yeast cells are affected by an oxidative stress situation demonstrated by increased protein carbonylation when compared with young cells. The data on the identification of these oxidatively modified proteins gives clues to better understand cellular dysfunction that occurs during aging. Strikingly, although in both aging models metabolic differences are important, major targets are almost the same. Common targets include stress resistance proteins (Hsp60 and Hsp70) and enzymes involved in glucose metabolism such as enolase, glyceraldehydes-3-P dehydrogenase, fructose-1,6-biphosphate aldolase, pyruvate decarboxylase, and alcohol dehydrogenase. In both aging models, calorie restriction results in decreased damage to these proteins. In addition, chronological-aged cells grown under glucose restriction displayed lowered levels of lipid peroxidation product lipofuscin. Intracellular iron concentration is kept almost unchanged, whereas in non-restricted cells, the values increase up 4-5 times. The pro-oxidant effects of such increased iron concentration would account for the damage observed. Also, calorie-restricted cells show undamaged catalase, which clearly appears carbonylated in cells grown at a high glucose concentration. These results may explain lengthening of the viability of chronological-aged cells and could have an important role in replicative life span extension by calorie restriction.

Cell Division↗
PubMed1996

[Evolution modes of eukaryote retrotransposons].

A number of general problems of molecular macroevolution of retroposons were examined, including the question of the ratio of the contributions of genomic replication and retrotransposition to mutational variability of retrotransposons, as well as that of the influence of stress-induced transpositional variability on the rate of evolution and the phylogenetic trees of retrotransposons. It is thought that the substitution fixation rate in genes of retrotransposons is determined by the transposition rate and the probability of mutation upon replication of copies of retransposons in the genome and upon retrotransposition, as well as by selection stabilizing the function of proteins of the retroreplicative mechanism. By means of molecular-evolutionary parameters, estimated for Drosophila retrotransposons and animal retroviruses, it was shown that spontaneous retrotransposition makes the dominant contribution to the frequency of mutation, and the expected fixation rate of nucleotide substations is on the order of 2 x 10(-8) per position per year. This version of evolution of retrotransposons agrees with the results of phylogenetic analysis of trees of macroevolution. Another version, associated with stress-induced transpositions, gives a very high rate of evolution, on the order 3 x 10(-6) fixations of nucleotide substitutions per position per year. This version seems improbable, as it leads to a significant hidden genetic load.

Animals↗
PubMed2006

Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma.

Evidence supporting the contribution of oxidative stress to key pathways in cancer, such as inflammation and DNA damage, continues to mount. We investigated variations within genes mediating oxidative stress to determine whether they alter risk for non-Hodgkin lymphoma (NHL). Thirteen single nucleotide polymorphisms (SNPs) from 10 oxidative stress genes (AKR1A1, AKR1C1, CYBA, GPX, MPO, NOS2A, NOS3, OGG1, PPARG and SOD2) were genotyped in 1172 NHL cases and 982 population-based controls from a USA multicenter case-control study. For NHL and five subtypes (diffuse large B-cell, follicular, marginal zone, small lymphocytic and T-cell), SNP associations were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for sex, age (<45, 45-64, 65+ years), race (white, black, other) and study site. Overall, the oxidative stress pathway was associated significantly with the B-cell NHL subtype, diffuse large B-cell lymphoma (DLBCL) (global P-value=0.003). Specifically, for nitric oxide synthase (NOS2A Ser608Leu, rs2297518) Leu/Leu homozygotes, there was a 2-fold risk increase for NHL (OR=2.2, 95% CI=1.1-4.4) (referent=Ser/Ser and Ser/Leu). This risk increase was consistent by cell lineage (B- and T-cell NHL) and pronounced for the two most common subtypes, diffuse large B-cell (OR=3.4, 95% CI=1.5-7.8) and follicular lymphoma (OR=2.6, 95% CI=1.0-6.8). In an analysis of manganese superoxide dismutase (SOD2 Val16Ala, rs1799725) Ala/Ala homozygotes, we observed moderately increased risks for B-cell lymphomas (OR=1.3, 95% CI=1.0-1.6; referent=Val/Val and Val/Ala) that was consistent across the B-cell subtypes. Genetic variations that result in an increased generation of reactive oxygen species appear to increase risk for NHL and its major subtypes, particularly DLBCL. Independent replication of our findings are warranted and further evaluation of oxidative stress in the context of inflammation, DNA repair and the induction of the NF-kappaB pathway may further reveal important clues for lymphomagenesis.

Adult↗
PubMed1999

The antiviral enzymes PKR and RNase L suppress gene expression from viral and non-viral based vectors.

Expression of transfected genes is shown to be suppressed by two intracellular enzymes, RNase L and protein kinase PKR, which function in interferon-treated cells to restrict viral replication. RNase L(-/-) or PKR(-/-) murine embryonic fibroblasts produced enhanced levels of protein from transfected genes compared with wild-type cells. Increased expression of exogenous genes in RNase L(-/-) cells correlated with elevated levels of mRNA and thus appeared to be due to enhanced mRNA stability. Plasmid encoding adenovirus VA RNAs was able to further enhance accumulation of the exogenous gene transcript and protein, even in cells lacking PKR. In contrast to the increased expression of transfected genes in cells lacking RNase L or PKR, expression of endogenous host genes was unaffected by the absence of these enzymes. In addition, a dominant-negative PKR mutant improved expression from a conventional plasmid vector and from a Semliki Forest virus derived, self-replicating vector. These results indicate that viral infections and transfections produce similar stress responses in mammalian cells and suggest strategies for selectively increasing expression of exogenous genes.

Adenoviridae↗
PubMed2002

Proteomic analysis of rice leaves during drought stress and recovery.

Three-week old plants of rice (Oryza sativa L. cv CT9993 and cv IR62266) developed gradual water stress over 23 days of transpiration without watering, during which period the mid-day leaf water potential declined to approximately -2.4 MPa, compared with approximately -1.0 MPa in well-watered controls. More than 1000 protein spots that were detected in leaf extracts by proteomic analysis showed reproducible abundance within replications. Of these proteins, 42 spots showed a significant change in abundance under stress, with 27 of them exhibiting a different response pattern in the two cultivars. However, only one protein (chloroplast Cu-Zn superoxide dismutase) changed significantly in opposite directions in the two cultivars in response to drought. The most common difference was for proteins to be up-regulated by drought in CT9993 and unaffected in IR62266; or down-regulated by drought in IR62266 and unaffected in CT9993. By 10 days after rewatering, all proteins had returned completely or largely to the abundance of the well-watered control. Mass spectrometry helped to identify 16 of the drought-responsive proteins, including an actin depolymerizing factor, which was one of three proteins detectable under stress in both cultivars but undetectable in well-watered plants or in plants 10 days after rewatering. The most abundant protein up-regulated by drought in CT9993 and IR62266 was identified only after cloning of the corresponding cDNA. It was found to be an S-like RNase homologue but it lacked the two active site histidines required for RNase activity. Four novel drought-responsive mechanisms were revealed by this work: up-regulation of S-like RNase homologue, actin depolymerizing factor and rubisco activase, and down-regulation of isoflavone reductase-like protein.

Actin Depolymerizing Factors↗
PubMed2004

Modulation of natural killer cell activity by restraint stress during an influenza A/PR8 infection in mice.

These experiments were designed to examine the influences of restraint stress (RST) on natural killer (NK) activity and to determine its consequences on influenza A/PR8 (A/PR8) viral replication in mice. The data showed that RST delayed the recruitment of NK1.1+ cells into the lung parenchyma during infection. Quantification of MIP-1alpha and MCP-1 gene expression by real-time PCR revealed that RST suppressed the chemokines responsible for NK cell recruitment into the infected tissue. Additionally, RST suppressed the expression of several macrophage-derived cytokines involved in the effector response of NK cells. IL-15, which is the main cytokine involved in NK cell development and homeostasis, and IL-12, which is important for NK cytotoxicity, were both suppressed. As the NK cell response is an important innate response to control viral replication, we hypothesized that the RST-mediated reduction in NK cell numbers and function would enable viral replication to continue unchecked. In fact, there was enhanced viral replication in the lungs of RST animals. Interestingly, expression of the anti-viral type I interferons (IFN-alpha and IFN-beta) was elevated presumably in response to the elevated viral load in the stressed mice. Together, these data show that RST suppressed expression of the cytokine genes involved in the recruitment and activation of NK cells during an experimental influenza viral infections. The consequence of this effect was diminished NK cell function and enhanced viral replication.

Adaptation, Physiological↗
PubMed1990

Discordance of physiological and biochemical response to smoking and to psychological stress.

Both smoking and psychological stress produce marked effects upon cardiovascular function, and several studies have demonstrated that in combination they produce additive or potentiating effects. More recently, it has been reported that individuals strongly reactive to psychological stress are also strongly reactive to nicotine. In an attempt to replicate and extend those findings, we examined reactivity to smoking and competitive mental arithmetic across several physiological and biochemical variables. Despite stable responding across mental arithmetic trials, we were unable to demonstrate significant correlations between reactivity to smoking and to a psychological stressor. We further observed that anxiety level, when low, was a poor predictor of desire to smoke and of withdrawal, whereas higher anxiety levels were more tightly linked to these measures. These findings have implications for the identification of individuals at risk of cardiovascular disease as well as for the design of smoking treatment and relapse prevention programs.

Adult↗
PubMed2002

Development of the chicken as a model for prenatal stress.

Exposing a pregnant mammal to stressors causes behavioral and physiological alterations in her offspring ("prenatal stress"); however, elucidation of the underlying mechanism is hindered by an inability to control maternal compounds that may affect the fetus. We designed this experiment to determine if the autonomously developing chicken embryo could be developed as a model for prenatal stress. On d 16 of incubation, eggs were treated with: 1) 60 ng corticosterone (CORT), 2) elevated incubation temperature (40.6 degrees C) for 24 h (HEAT), or 3) no treatment (Control). Chicks from all three treatments hatched at similar weights; however, HEAT chicks weighed less by 100 d of age and remained lighter until the end of the study (P < 0.05). At 8 d post-beak trimming, adrenal gland weight was not different (P > 0.20) among treatments, basal plasma corticosterone concentrations tended (P < 0.06) to be greater for CORT chicks than either the Control or HEAT chicks, and CORT chicks were heavier than HEAT chicks (P < 0.005) but not Control chicks (P > 0.20). At 11-wk, HEAT birds had heavier adrenal glands than did Control birds (P < 0.01). At 16 wk of age, Control cocks performed more (P < 0.01) pecking aggression than either HEAT or CORT cocks, whereas CORT cocks were chased more often and chased another cock less often than either HEAT or Control cocks (P < 0.01). Treatments did not alter the behavior of the hens (P > 0.10). Administration of corticosterone during incubation replicated some, but not all, of the effects seen in prenatal stress in mammals.

Adrenal Glands↗
PubMed2026

Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence.

Cellular senescence is a state of irreversible cell cycle arrest triggered by telomere erosion, persistent DNA damage or chronic stress. The accumulation of senescent cells disrupts tissue function and contributes to aging and disease. Here, we employ mass spectrometry-based proteomics to systematically interrogate dynamic proteome changes at multiple levels during the progression of replicative cellular senescence. We demonstrate that proteome changes during senescence occur in a coordinated manner, characterized by widespread protein depletion on chromatin. Moreover, components of the cytoplasmic translation machinery are depleted, while mitochondrial proteins display increased insolubility. Autophagic and proteasome activity is compromised in senescent cells along with remodeling of ubiquitin linkages and depletion of ubiquitin E3 ligases. Comparison of the senescent proteome with different pathophysiological cellular states reveals a distinctive senescent signature shaped by changes in the proteostasis network. Collectively, we provide a resource for the exploration of temporally resolved changes in the senescent proteome.

Cellular Senescence↗