Biomedical subjects

Yunping Zhu

Publications and source records attributed to Yunping Zhu.

At least 19 recordsLinked to original sources

PubMed2026

AI proteomics: from protein identification to virtual cells.

Artificial intelligence (AI) is transforming scientific research, including proteomics. In this Perspective, we highlight key mass spectrometry (MS)-based proteomics areas where AI is driving innovation, ranging from protein identification to building AI virtual cells. These include improving peptide and protein identification and quantification; characterizing protein-protein interactions and protein complexes; advancing spatial and perturbation proteomics; integrating multi-omics data; and, ultimately, enabling AI virtual cells. Finally, we call for global collaboration among data producers, data consumers and other stakeholders to establish an AI-friendly ecosystem for MS-based proteomics, laying the foundation for transformative advancements in proteomics driven by AI.

Proteomics↗

PubMed2006

SigFlux: a novel network feature to evaluate the importance of proteins in signal transduction networks.

BACKGROUND: Measuring each protein's importance in signaling networks helps to identify the crucial proteins in a cellular process, find the fragile portion of the biology system and further assist for disease therapy. However, there are relatively few methods to evaluate the importance of proteins in signaling networks. RESULTS: We developed a novel network feature to evaluate the importance of proteins in signal transduction networks, that we call SigFlux, based on the concept of minimal path sets (MPSs). An MPS is a minimal set of nodes that can perform the signal propagation from ligands to target genes or feedback loops. We define SigFlux as the number of MPSs in which each protein is involved. We applied this network feature to the large signal transduction network in the hippocampal CA1 neuron of mice. Significant correlations were simultaneously observed between SigFlux and both the essentiality and evolutionary rate of genes. Compared with another commonly used network feature, connectivity, SigFlux has similar or better ability as connectivity to reflect a protein's essentiality. Further classification according to protein function demonstrates that high SigFlux, low connectivity proteins are abundant in receptors and transcriptional factors, indicating that SigFlux candescribe the importance of proteins within the context of the entire network. CONCLUSION: SigFlux is a useful network feature in signal transduction networks that allows the prediction of the essentiality and conservation of proteins. With this novel network feature, proteins that participate in more pathways or feedback loops within a signaling network are proved far more likely to be essential and conserved during evolution than their counterparts.

Adaptor Proteins, Signal Transducing↗

PubMed2006

A dataset of human fetal liver proteome identified by subcellular fractionation and multiple protein separation and identification technology.

A high throughput process including subcellular fractionation and multiple protein separation and identification technology allowed us to establish the protein expression profile of human fetal liver, which was composed of at least 2,495 distinct proteins and 568 non-isoform groups identified from 64,960 peptides and 24,454 distinct peptides. In addition to the basic protein identification mentioned above, the MS data were used for complementary identification and novel protein mining. By doing the analysis with integrated protein, expressed sequence tag, and genome datasets, 223 proteins and 15 peptides were complementarily identified with high quality MS/MS data.

Cell Membrane↗

PubMed2006

Multi-modality of pI distribution in whole proteome.

Multi-modality of pI distribution is a common feature in different whole proteomes. Some researchers considered it relate to the proteins with different subcellular locations, indicating the result of natural selection. We explored the pI distribution of predicted proteomes (including animals, plants, bacterium, archaeans) and random proteome [random protein sequences constructed according to the special amino acid composition and molecular weight (MW) distribution of human predicted proteome]. Our results suggest that the multi-modality is the result of discrete pK(R) values for different amino acids. Amino acid composition and MW distribution of a proteome also contributes to the specific pI distribution. Although protein subcellular location was related to pI value, our analyses revealed that comparing with the random proteome, neither the multi-modality phenomenon nor the distribution bias of pI values is caused by subcellular location. It seems that the multi-modality distribution is just a mathematical fun. The blank region near the neutral pI was caused by the absence of amino acids with neutral pK(R), and suggests that the selection of amino acids with ionizable side chain might be restricted by the requirement for a special pH environment during the origin of life. From this point of view, the special distribution was the result of natural selection.

Animals↗

PubMed2006

Protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster: large-scale organization and robustness.

High-throughput screens have begun to reveal protein interaction networks in several organisms. To understand the general properties of these protein interaction networks, a systematic analysis of topological structure and robustness was performed on the protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. It shows that the three protein interaction networks have a scale-free and high-degree clustering nature as the consequence of their hierarchical organization. It also shows that they have the small-world property with similar diameter at 4-5. Evaluation of the consequences of random removal of both proteins and interactions from the protein interaction networks suggests their high degree of robustness. Simulation of a protein's removal shows that the protein interaction network's error tolerance is accompanied by attack vulnerability. These fundamental analyses of the networks might serve as a starting point for further exploring complex biological networks and the coming research of "systems biology".

Algorithms↗

PubMed2006

Inflammation inhibitors were remarkably up-regulated in plasma of severe acute respiratory syndrome patients at progressive phase.

Severe acute respiratory syndrome (SARS) is a severe infectious disease that has affected many countries and regions since 2002. A novel member of the coronavirus, SARS-CoV, has been identified as the causative agent. However, the pathogenesis of SARS is still elusive. In this study, we used 2-D DIGE and MS to analyze the protein profiles of plasma from SARS patients, in the search for proteomic alterations associated with the disease progression, which could provide some clues to the pathogenesis. To enrich the low-abundance proteins in human plasma, two highly abundant proteins, albumin and IgG, were first removed. By comparing the plasma proteins of SARS patients with those of a normal control group, several proteins with a significant alteration were found. The up-regulated proteins were identified as alpha-1 acid glycoprotein, haptoglobin, alpha-1 anti-chymotrypsin and fetuin. The down-regulated proteins were apolipoprotein A-I, transferrin and transthyretin. Most of the proteins showed significant changes (up- or down-regulated) in the progressive phase of disease, and there was a trend back to normal level during the convalescent phase. Among these proteins, the alterations of fetuin and anti-chymotrypsin were further confirmed by Western blotting. Since all the up-regulated proteins identified above are well-known inflammation inhibitors, these results strongly suggest that the body starts inflammation inhibition to sustain the inflammatory response balance in the progression of SARS.

Adult↗

PubMed2006

Protein probabilities in shotgun proteomics: evaluating different estimation methods using a semi-random sampling model.

The calculation of protein probabilities is one of the most intractable problems in large-scale proteomic research. Current available estimating methods, for example, ProteinProphet, PROT_PROBE, Poisson model and two-peptide hits, employ different models trying to resolve this problem. Until now, no efficient method is used for comparative evaluation of the above methods in large-scale datasets. In order to evaluate these various methods, we developed a semi-random sampling model to simulate large-scale proteomic data. In this model, the identified peptides were sampled from the designed proteins and their cross-correlation scores were simulated according to the results from reverse database searching. The simulated result of 18 control proteins was consistent with the experimental one, demonstrating the efficiency of our model. According to the simulated results of human liver sample, ProteinProphet returned slightly higher probabilities and lower specificity than real cases. PROT_PROBE was a more efficient method with higher specificity. Predicted results from a Poisson model roughly coincide with real datasets, and the method of two-peptide hits seems solid but imprecise. However, the probabilities of identified proteins are strongly correlated with several experimental factors including spectra number, database size and protein abundance distribution.

Chromatography, Liquid↗

PubMed2006

Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China.

OBJECTIVES: Aflatoxin B1 exposure is one of the major risk factors for hepatocellular carcinoma (HCC). CYP1A2 is a cytochrome P450 isoenzyme that plays an important role in the bioactivation of AFB1 to its carcinogenic metabolite. The study was designed to assess whether genetic polymorphisms in CYP1A2 are associated with HCC susceptibility in a high-risk region. METHODS: A case-control study of 431 HCC cases and 550 cancer-free controls recruited from an HCC endemic region in China was carried out. Three single nucleotide polymorphisms, namely -3860G > A (CYP1A2*1C), -3113G > A, and 5347T > C (CYP1A2*1B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Homozygous carriers of the major haplotype -3860G/-3113G/5347C were associated with increased HCC susceptibility in the overall population (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.11-2.46, P = 0.014), in HBsAg seronegative individuals (OR = 2.69, 95% CI: 1.43-5.06, P = 0.002), and in heavy smokers (OR = 2.14, 95% CI: 1.21-3.80, P=0.009). In addition, individuals carrying at least one CYP1A2*1C allele showed significantly decreased HCC risk (OR = 0.49, 95% CI: Q0.27-0.86, P = 0.013) in the HBsAg seronegative subpopulation. Furthermore, as compared with HBsAg seropositive patients, wild-type homozygotes of the CYP1A2*1C polymorphism were significantly over-represented in HBsAg seronegative patients (P = 0.024). No significant association between CYP1A2 genetic polymorphisms and HCC risk was observed in either HBsAg seropositive individuals or non-smokers. CONCLUSIONS: CYP1A2 genetic polymorphisms are associated with HCC susceptibility in smokers and HBsAg seronegative individuals in the Fusui endemic region.

Adult↗

PubMed2005

CKIP-1 recruits nuclear ATM partially to the plasma membrane through interaction with ATM.

CKIP-1 (casein kinase-2 interacting protein-1) is implicated in muscle differentiation, regulation of cell morphology and actin cytoskeleton. More recently, we showed that CKIP-1 regulated AP-1 activity and promoted apoptosis via caspase-3-dependent cleavage and translocation. Here, we report that overexpression of CKIP-1 in SK-BR-3 breast cancer cells prevents p53 degradation induced by cycloheximide treatment through increase of p53 N-terminal Ser-15 phosphorylation level. CKIP-1 could interact with ATM, which is an upstream kinase of p53, thereby enhance the stability of p53. Interestingly, CKIP-1 is localized both at the plasma membrane and in the nucleus dependent on the cell types, and only the plasma membrane-localized CKIP-1 could form a complex with ATM. Importantly, CKIP-1 recruits nuclear ATM proteins partially to the plasma membrane. Our data provide the first evidence that ATM, a predominantly nuclear kinase, could be relocalized to the plasma membrane by CKIP-1 and shed new light on the multi-functional CKIP-1.

Animals↗

PubMed2005

Association between mannose-binding lectin gene polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus infection.

BACKGROUND: Genetic determinants of susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV) infection remain unknown. We assessed whether mannose-binding lectin (MBL) gene polymorphisms were associated with susceptibility to SARS-CoV infection or disease severity in an ethnically homogeneous population born in northern China. METHODS: The frequencies of 1 mutation in codon 54 and 3 promoter polymorphisms at nt -550, -221, and 4 were ascertained in 352 patients with SARS and 392 control subjects, by means of polymerase chain reaction direct sequencing. RESULTS: Of 352 patients with SARS and 392 control subjects, 120 (34.4%) and 91 (23.2%) were carriers of the codon 54 variant, respectively (odds ratio [OR], 1.73 [95% confidence interval {CI}, 1.25-2.39]; P=.00086). A total of 123 (36.0%) of 352 patients with SARS and 100 (25.5%) of 392 control subjects had haplotype pairs associated with medium or low expression of MBL (OR, 1.67 [95% CI, 1.21-2.29]; P=.00187). The population-attributable fraction of patients with SARS that was associated with having the codon 54 variant was 20.1% (95% CI, 7.9%-32.3%). CONCLUSIONS: MBL gene polymorphisms were significantly associated with susceptibility to SARS-CoV infection; this might be explained by the reduced expression of functional MBL secondary to having the codon 54 variant.

Alleles↗

PubMed2005

Role for the pleckstrin homology domain-containing protein CKIP-1 in AP-1 regulation and apoptosis.

The oncogenic transcription factor c-Jun plays an important role in cell proliferation, transformation and differentiation. All identified c-Jun-interacting proteins are localized to the nucleus or cytoplasm and function in their intact forms. Here we show that the pleckstrin homology domain-containing protein CKIP-1 (casein kinase 2-interacting protein-1) functions as a plasma membrane-bound AP-1 regulator. During apoptosis, CKIP-1 is cleaved by caspase-3 and translocated to the cytoplasm and then to the nucleus. C-terminal fragments of cleaved CKIP-1 strongly repress AP-1 activity. Importantly, CKIP-1 overexpression promotes apoptosis by forming a positive feedback loop between CKIP-1 and caspase-3. RNA interference of CKIP-1 or overexpression of c-Jun attenuates the sensitivity to apoptosis, indicating a novel role of CKIP-1 in apoptosis. CKIP-1 is the first case of a c-Jun-interacting protein that regulates AP-1 activity via caspase-3-dependent cleavage and translocation.

Animals↗

PubMed2005

The G-113A polymorphism in CYP1A2 affects the caffeine metabolic ratio in a Chinese population.

OBJECTIVE: This study was designed to better understand genetic variation in the cytochrome P450 (CYP) gene CYP1A2 and its impact on CYP1A2 activity in Chinese subjects. METHODS: CYP1A2 genetic polymorphisms were screened by direct sequencing in 27 selected Chinese subjects. Plasma 1,7-dimethylxanthine/caffeine ratios 5 hours after a 100-mg caffeine administration, used as an index of CYP1A2 in vivo activity, were determined in 422 healthy subjects. Five single-nucleotide polymorphism markers, including G-860A (CYP1A2*1C), T-3594G, G-3113A, A-163C (CYP1A2*1F), and C5347T (CYP1A2*1B), were selected and genotyped by either polymerase chain reaction-restriction fragment length polymorphism or direct sequencing. RESULTS: Thirteen polymorphisms and 2 linkage disequilibrium blocks with a boundary around -2467 were identified at this locus. The allele frequency for -3860A, -3594G, -3113A, -163C, and 5347T was 0.21, 0.15, 0.10, 0.36, and 0.14, respectively, in the CYP1A2-phenotyped cohort. A significant difference in CYP1A2 activity was observed among genotypes of polymorphism G-3113A (P = .038), and CYP1A2 activity in subjects carrying the AA genotype was lower than that in those carrying the GA (P = .096) and GG genotypes (P = .036): -0.45 +/- 0.05 (mean +/- SD), -0.32 +/- 0.16, and -0.29 +/- 0.16, respectively. Further analysis based on haplotype pairs found a 1.92-fold variation (95% confidence interval, 1.13-2.71) in mean CYP1A2 activity between haplotype pairs 13 and 15, and the difference was significant (-0.19 +/- 0.15 versus -0.45 +/- 0.05, P = .016). As compared with haplotype pair 10, haplotype pairs 9 and 15 and most haplotype pairs heterozygous for the haplotype with an A allele at -3113, including pairs 5, 8, and 12, also showed significantly lower CYP1A2 activity (P = .015, .048, .008, .024, and .014 for pairs 5, 8, 9, 12, and 15, respectively). In addition, haplotype pairs 5, 9, and 12 also showed significantly lower CYP1A2 activity than pair 13 (P = .034, .020, and .037 for pairs 5, 9, and 12, respectively). CONCLUSIONS: The G-3113A polymorphism is associated with decreased CYP1A2 activity, haplotype pairs 10 and 13 are responsible for high CYP1A2 activity, and haplotype pairs 5, 8, 9, 12, and 15 are responsible for low CYP1A2 activity in Chinese subjects.

Adolescent↗

PubMed2005

Radiation treatment for medulloblastoma: a review of 64 cases at a single institute.

BACKGROUND: Although the optimal treatment mode for medulloblastoma is frequently discussed, results based on large series of cases, especially those treated in Asia, have rarely been reported. Our purpose was to evaluate the efficacy of postoperative radiation therapy, and to identify prognostic factors, in a relatively large cohort of patients with limited-stage medulloblastoma treated at a single institute in China. METHODS: Between January 1996 and April 2001, 69 patients with Chang stage M0/M1 medulloblastoma were referred to our hospital for radiation therapy after total or subtotal resection of the primary tumor. All patients received 30 Gy to the craniospinal axis followed by a 20-25 Gy boost to the posterior fossa (median fraction, 1.8 Gy). RESULTS: Sixty-four patients were followed for a median period of 38.5 months. The rates of 3-year and 5-year overall survival were 68.8% and 55.7%, respectively; corresponding disease-free survival were 57.8% and 51.4%, respectively. Patients who had received radiation treatment within 25 days after resection had a greater probability of 3-year survival (81.5% versus 59.5%; P = 0.11) and 3-year disease-free survival (74.1% versus 46.0%; P = 0.03) than patients who began radiation treatment later. No relationship was found between survival and age, sex or tumor size. CONCLUSIONS: This regimen was comparatively ineffective in preventing recurrence of postoperative medulloblastoma; however, we found that the interval between surgery and radiation is a significant prognostic factor for disease-free survival.

Adolescent↗

PubMed2004

Direct association of hepatopoietin with thioredoxin constitutes a redox signal transduction in activation of AP-1/NF-kappaB.

It has been demonstrated that growth factors quiescin Q6 family was created by the fusion of the sulfhydryl oxidase fragment of the yeast essential for respiration and vegetative growth (ERV)1 prototype [an orthologue of hepatopoietin (HPO)] and thioredoxin (TRX)/disulfide isomerase domain during evolution. In this paper, our results demonstrated that two components of this composite protein, i.e., HPO and TRX, were involved in the same signal transduction and interacted physically in eukaryocyte. When HPO and TRX were cotransfected into COS7 cells, the activity of activator protein-1 (AP-1) and NF-kappaB was evidently enhanced compared with the transfection with HPO or TRX alone, at the same time, the phosphorylation of c-Jun was increased. They were colocalized in the cells. By Co-IP and GST pull-down experiments, we found that HPO could physically interact with TRX, which was also confirmed by yeast two-hybrid assay. By further investigation, we found both HPO and TRX were sensitive to cellular oxidative state. HPO dimer is in its natural state and could be reduced by dithiothreitol (DTT) in vitro and in vivo. Under the treatment of oxidants such as H(2)O(2) and diamide, the amount of HPO monomer was decreased significantly and assembled into dimer, and the free thiol in TRX was oxidized. HPO could transfer oxidizing equivalents to TRX via direct thiol-disulfide exchange in vitro, the redox state of TRX was also affected by HPO in vivo. Taken together, it was implicated that the oxidizing equivalents might flow from HPO to TRX and then to substrate protein by the dimerization of HPO, and its interaction with TRX finally activates the redox-sensitive transcription factor, suggesting a new redox signal pathway conducted by thiol-disulfide transformation in eukaryocytic cytoplasm.

Animals↗

PubMed2004

Macrophage migration inhibitory factor directly interacts with hepatopoietin and regulates the proliferation of hepatoma cell.

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine involved in inflammation and immune responses as well as in growth factor-dependent cell proliferation, cell cycle, angiogenesis, and tumorigenesis. Several studies have documented MIF expression in the sera following hepatic resection or in the course of liver cancer progression, but there is a paucity of information regarding the effect of MIF on hepatoma cells and relating mechanisms. In this paper, by [3H] thymidine incorporation, we found that exogenously added MIF could promote the proliferation of HepG2 in a dose-dependent manner. Hepatopoietin (HPO), as a liver-specific regeneration augmenter, could be induced by the expression of MIF in hepatoma cells. The activity of HPO promoter was increased, and its levels were enhanced after MIF was overexpressed in hepatoma cells. The similarities between HPO and MIF in structure and action led us to investigate their interaction and the inducing biological significance. Using yeast two-hybrid identification, we found that HPO interacted with MIF in yeast cells, and their binding ability was higher than that between HPO and JAB1 (Jun activation domain binding protein) or MIF and JAB1 in yeast cells. Their interaction was further verified by His pull-down assay in vitro and coimmunoprecipitation experiment in vivo. They were colocalized in the cytoplasm. Both HPO and MIF could bind to JAB1 and modulate the AP-1 pathway. When HPO and MIF were cotransfected into HepG2 cells, the binding activity of MIF to JAB1 was reduced, and the activity of AP-1 was improved. In contrast, MIF overexpressed in HepG2 was unable to interfere with the binding activity of HPO to JAB1, but its potentiation on AP-1 activity was reduced significantly. Taken together, these results indicate that MIF plays an important role in the proliferation of hepatoma cells, and the effect of MIF is in concert with HPO.

COP9 Signalosome Complex↗

PubMed2004

Transglycosylation reaction of xylanase B from the hyperthermophilic Thermotoga maritima with the ability of synthesis of tertiary alkyl beta-D-xylobiosides and xylosides.

The recombinant xylanase B (XynB) of Thermotoga maritima MSB8 was characterized and was found to cleave p-nitrophenyl beta-D-xyloside via the transglycosylation reaction in the previous study. XynB was activated in the presence of alcohols, and XynB activity was increased by iso-propanol (2M) to 2.1-fold. This type of activation was investigated and was shown to be due to the transglycosylation activity with p-nitrophenyl beta-D-xylobioside being converted to alkyl beta-D-xylobiosides in the presence of XynB and alcohols. Through the transglycosylation reaction, alkyl beta-xylosides and xylobiosides were simultaneously produced in the presence of xylan and alcohols. Primary alcohols were found to be the best acceptors. The highest yields of alkyl beta-xylosides and xylobiosides were 33% and 50% of the total sugar, respectively. XynB showed a great ability to transfer xylose and xylobiose to secondary alcohol acceptors, and was unique for being able to synthesize the tertiary alkyl beta-xylosides and xylobiosides with high yields of 18.2% and 11.6% of the total sugar, respectively. This is the first report of a xylanase with the ability to synthesize tertiary alkyl beta-xylosides and xylobiosides. The specificity of the beta-linkage was confirmed by the proton nuclear magnetic resonance ((1)H NMR). Thus, XynB of T. maritima appears to be an ideal enzyme for the synthesis of useful alkyl beta-xylosides and xylobiosides.

Alkylation↗

PubMed2004

Characterization of Ceap-11 and Ceap-16, two novel splicing-variant-proteins, associated with centrosome, microtubule aggregation and cell proliferation.

A novel human gene, encoding two polypeptide-isoforms, has been identified from human fetal liver cDNA library. These two alternatively spliced polypeptide-variants are associated with centrosomes, and are designated Ceap-11 and Ceap-16, respectively, according to the acronym Ceap for centrosomal-associated protein and the approximate relative molecular mass. The high degree of sequence similarity between Ceap proteins of divergent species indicates that the Ceap homologous genes are significantly conserved in evolution and constitute a new gene family without any functional information until now. Human Ceap gene is mapped on 10q24.2. These two Ceap cDNA isoforms are generated by RNA alternative splicing on the 5' terminus of the Ceap gene, and are composed of four and five exons, respectively. Ceap-11 and Ceap-16 are co-immunoprecipitated and co-located with gamma-tubulin; ectopic overexpression of these two proteins in NIH3T3 cells induces microtubule aggregation and cell proliferation; the protein level of Ceap in certain tumors is significantly higher than that in corresponding normal tissues. Taken together, our data provide the first evidence for the function of Ceap-11 and Ceap-16, the two novel human proteins, namely, association with centrosome, microtubule aggregation and cell proliferation.

Alternative Splicing↗

PubMed2004

Hepatopoietin interacts directly with COP9 signalosome and regulates AP-1 activity.

Hepatopoietin (HPO)/augmenter of liver regeneration (ALR) is a specific hepatotrophic growth factor, which plays a key role in liver regeneration. Our previous study indicated that HPO executes its function by an inter-reactive network of the autocrine, paracrine and endocrine pathways. Recently, we have demonstrated that intracellular HPO interacts with Jun activation domain-binding protein 1 (JAB1) and leads to potentiation of activating protein-1 (AP-1) activity in a MAPK independent fashion. JAB1 is the fifth subunit of the COP9 signalosome (CSN), which is first identified as a suppressor of plant morphogenesis. A protein complex kinase activity associated with the CSN has been reported but not identified yet. In this report, we investigated further the association of HPO with the whole CSN. HPO exists in a complex with the eight-component CSN, both when purified from glycerol gradient centrifugation and when reciprocal immunoprecipitated from the lysates of transfected COS-7 cells. Intracellular HPO colocalizes with endogenous CSN in nucleus of hepatic cells. In addition, intracellular function of HPO that increases the phosphorylation of c-Jun leading to potentiate the AP-1 activity is inhibited by curcumin, a potent inhibitor of CSN-associated kinase. Taken together, these results elucidate a novel relationship of intracellular growth factor, HPO with large protein complex, CSN, which suggests a possible linkage between CSN and liver regeneration.

Animals↗