When our knowledge of a field accumulates to a certain level,we are bound to see the rise of one or more great scientists.They will make a series of grand discoveries/breakthroughs and push the discipline into an '...When our knowledge of a field accumulates to a certain level,we are bound to see the rise of one or more great scientists.They will make a series of grand discoveries/breakthroughs and push the discipline into an 'age of grand discoveries'.Mathematics,geography,physics and chemistry have all experienced their ages of grand discoveries;and in life sciences,the age of grand discoveries has appeared countless times since the 16th century.Thanks to the ever-changing development of molecular biology over the past 50 years,contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be 'lifeomics'.At the end of the 20th century,genomics wrote out the 'script of life';proteomics decoded the script;and RNAomics,glycomics and metabolomics came into bloom.These 'omics',with their unique epistemology and methodology,quickly became the thrust of life sciences,pushing the discipline to new high.Lifeomics,which encompasses all omics,has taken shape and is now signalling the dawn of a new era,the age of grand discoveries.展开更多
Analysis of the mitochondrial proteome would provide valuable insight into the function of this important organelle, which plays key roles in energy metabolism, apoptosis, free radical production, thermogenesis, and c...Analysis of the mitochondrial proteome would provide valuable insight into the function of this important organelle, which plays key roles in energy metabolism, apoptosis, free radical production, thermogenesis, and calcium signaling. It could also increase our understanding about the mechanisms that promote mitochondrial disease. To identify proteins that are antigenically dominant in human liver mitochondria, we generated >240 hybridoma cell lines from native mitochondrial proteins after cell fusion, screening, and cloning. Antibodies that recognized mitochondrial proteins were identified by screening human liver cDNA expression libraries. In this study, we identified 6 major antigens that were recognized by at least 2 different monoclonal antibodies (mAbs). The proteins that were antigenically dominant were: acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase), aldehyde dehydrogenase 1 family member A1, carbamoyl phosphate synthetase 1, dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase complex), enoyl coenzyme A hydratase 1, and hydroxysteroid (11-beta) dehydrogenase 1. We also determined the subcellular localizations of these enzymes within the mitochondria using immunohistocytochemistry. We believe that these well-characterized antibodies will provide a valuable resource for the Human Liver Proteome Project (HLPP), and will make studies aimed at investigating liver mitochondrial function far easier to perform in future. Our results provide strong evidence that, (i) depletion of dominant proteins from liver mitochondrial samples is possible and, (ii) the approaches adopted in this study can be used to explore or validate protein-protein interactions in this important organelle.展开更多
A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease,treatment decisions,and assessing drug efficacy.This study evaluated plasma proteomic profiling via an N-terminal isotope t...A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease,treatment decisions,and assessing drug efficacy.This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging.Pooled plasma from different liver fibrosis stages,which were assessed in advance by the current gold-standard of liver biopsy,was quantitatively analyzed.A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process,and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis.Validation results of fibronectin by Western blotting reconfirmed the mass-based data.Ingenuity Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B patients.Consequently,quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver fibrosis.We quantitatively monitored the fibrogenesis process in CHB patients.We discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis disease.These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.展开更多
The tumor suppressor p53 locates at the key point of cell growth or apoptosis balance, and the expression level of p53 is tightly controlled by ubiquitin ligases including MDM2. Upon DNA damage stresses, p53 was accum...The tumor suppressor p53 locates at the key point of cell growth or apoptosis balance, and the expression level of p53 is tightly controlled by ubiquitin ligases including MDM2. Upon DNA damage stresses, p53 was accumulated and activated, leading to cell cycle arrest or apoptosis. We previously showed that Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by interacting with and stabilizing MDM2, and consequently enhancing MDM2-mediated ubiquitylation of p53. However, it is unclear how the Smurf1-MDM2 interaction is regulated in response to DNA damage stress. Here, we show that in response to etoposide treatment Smurf1 dissociates from MDM2, resulting in MDM2 destabilization and p53 accumulation. The negative regulation of Smurf1 on apoptosis is released. Notably, this dissociation is a slow process rather than a rapid response, implicating high expression of Smurf1 might confer the resistance against p53 activation. Consistent with this notion, we observed that Smurf1/2 ligases are highly expressed in colon cancer, esophageal squamous cell carcinoma and pancreatic cancer tissues, suggesting the oncogenic tendency of Smurf1/2.展开更多
Functional proteomics can be defined as a strategy to couple proteomic information with biochemical and physiological analyses with the aim of understanding better the functions of proteins in normal and diseased orga...Functional proteomics can be defined as a strategy to couple proteomic information with biochemical and physiological analyses with the aim of understanding better the functions of proteins in normal and diseased organs.In recent years,a variety of publicly available bioinformatics databases have been developed to support protein-related information management and biological knowledge discovery.In addition to being used to annotate the proteome,these resources also offer the opportunity to develop global approaches to the study of the functional role of proteins both in health and disease.Here,we present a comprehensive review of the major human protein bioinformatics databases.We conclude this review by discussing a few examples that illustrate the importance of these databases in functional proteomics research.展开更多
Proteomics is a new science that focuses on the comprehensive analysis of proteins in intact organisms or in molecule machineries, organelles, cells, tissues, or organs. It has become an important area of interests in...Proteomics is a new science that focuses on the comprehensive analysis of proteins in intact organisms or in molecule machineries, organelles, cells, tissues, or organs. It has become an important area of interests in life sciences and has propelled the rapid development of cutting-edge biotechnology in展开更多
Integration of pathway and protein-protein interaction(PPI) data can provide more information that could lead to new biological insights. PPIs are usually represented by a simple binary model, whereas pathways are rep...Integration of pathway and protein-protein interaction(PPI) data can provide more information that could lead to new biological insights. PPIs are usually represented by a simple binary model, whereas pathways are represented by more complicated models. We developed a series of rules for transforming protein interactions from pathway to binary model, and the protein interactions from seven pathway databases, including PID, Bio Carta, Reactome, Net Path, INOH, SPIKE and KEGG, were transformed based on these rules. These pathway-derived binary protein interactions were integrated with PPIs from other five PPI databases including HPRD, Int Act, Bio GRID, MINT and DIP, to develop integrated dataset(named Path PPI). More detailed interaction type and modification information on protein interactions can be preserved in Path PPI than other existing datasets. Comparison analysis results indicate that most of the interaction overlaps values(OAB) among these pathway databases were less than 5%, and these databases must be used conjunctively. The Path PPI data was provided at http://proteomeview. hupo.org.cn/Path PPI/Path PPI.html.展开更多
The molecular evolutionary tree, also known as a phylogenetic tree, of the serine proteinase superfamily was constructed by means of structural alignment. Three-dimensional structures of proteins were aligned by the S...The molecular evolutionary tree, also known as a phylogenetic tree, of the serine proteinase superfamily was constructed by means of structural alignment. Three-dimensional structures of proteins were aligned by the SSAP program of Orengo and Taylor to obtain evolutionary distances. The resulting evolutionary tree provides a topology graph that can reflect the evolution of structure and function of homology proteinase. Moreover, study on evolution of the serine proteinase superfamily can lead to better understanding of the relationship and evolutionary difference among proteins of the superfamily, and is of significance to protein engineering, molecular design and protein structure prediction. Structure alignment is one of the useful methods of research on molecular evolution of protein.展开更多
The Chinese Academy of Sciences held its 7th forum on frontiers of Science and Technology,April 12-13,2012,in the academy hall of the Chinese Academy of Sciences.The Forum was organized by the Life Science and Medicin...The Chinese Academy of Sciences held its 7th forum on frontiers of Science and Technology,April 12-13,2012,in the academy hall of the Chinese Academy of Sciences.The Forum was organized by the Life Science and Medicine Division and co-organized by Academy of Military Medical Sciences and Science China Press.The theme of the 7th Forum was "Lifeomics and Translational Medicine",and the purpose was to discuss the significance of lifeomics(i.e.,展开更多
With the developments of international human transcriptome data and our ESTs of human fetal liver aged 22 weeks (wk) of gestation (HFL22w), the former research must be renewed. In this work, the EST data were firstly ...With the developments of international human transcriptome data and our ESTs of human fetal liver aged 22 weeks (wk) of gestation (HFL22w), the former research must be renewed. In this work, the EST data were firstly clustered by blasting against the ESTs of HFL22w, UniGene, DoTS, MGC and Twinscan-predicted human transcriptome. Then, after EST assembly and gene identification, the known genes were classified by GO (gene ontology), and the unknown genes were predicted by Pfam and ScanProsite to clarify their functions. In the end, the relations of 5 tissues including fetal liver, adult liver, bone marrow, thymus and lymph node that possess hemopoiesis or can indicate fetal liver characteristics were analyzed by hierarchical clustering. The results show that: (i) By comparing the 5 newest human transcriptome databases, we can largely reduce the probability that the ESTs belonging to unconnected parts of one gene were probably divided into different clusters, so it is recommended to blast against the newest databases when clustering EST data; (ii) some previous unknown ESTs had been identified as function-known genes, and 1379 genes were identified as fully new sequences possessed in our lab; (iii) through GO classification, we got a rough understanding of HFL22w, and obtained 6 cell migration genes and 6 hemopoiesis genes; (iv) prediction of gene function had enabled us to obtain 277 profiles, among them, there are 5 categories distributed in more than 10 genes; (v) five tissue relations analyzed by hierarchical clustering are related to their functions; (vi) We have built the world's largest EST database on HFL22w. Renewal and preliminary analysis of EST database on HFL22w will help to understand hemopoiesis and cell migration mechanism, and promote future research on human fetal liver.展开更多
基金funded by China-Australia Joint Science and Technology Commission (2010DFA31260)China-Canada Joint Health Research Initiative (81010064)
文摘When our knowledge of a field accumulates to a certain level,we are bound to see the rise of one or more great scientists.They will make a series of grand discoveries/breakthroughs and push the discipline into an 'age of grand discoveries'.Mathematics,geography,physics and chemistry have all experienced their ages of grand discoveries;and in life sciences,the age of grand discoveries has appeared countless times since the 16th century.Thanks to the ever-changing development of molecular biology over the past 50 years,contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be 'lifeomics'.At the end of the 20th century,genomics wrote out the 'script of life';proteomics decoded the script;and RNAomics,glycomics and metabolomics came into bloom.These 'omics',with their unique epistemology and methodology,quickly became the thrust of life sciences,pushing the discipline to new high.Lifeomics,which encompasses all omics,has taken shape and is now signalling the dawn of a new era,the age of grand discoveries.
基金supported by the National Basic Research Program of China (Grant No. 2006CB910803)the National High Technology Research and Development Program of China (Grant No. 2006AA02A311)
文摘Analysis of the mitochondrial proteome would provide valuable insight into the function of this important organelle, which plays key roles in energy metabolism, apoptosis, free radical production, thermogenesis, and calcium signaling. It could also increase our understanding about the mechanisms that promote mitochondrial disease. To identify proteins that are antigenically dominant in human liver mitochondria, we generated >240 hybridoma cell lines from native mitochondrial proteins after cell fusion, screening, and cloning. Antibodies that recognized mitochondrial proteins were identified by screening human liver cDNA expression libraries. In this study, we identified 6 major antigens that were recognized by at least 2 different monoclonal antibodies (mAbs). The proteins that were antigenically dominant were: acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase), aldehyde dehydrogenase 1 family member A1, carbamoyl phosphate synthetase 1, dihydrolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase complex), enoyl coenzyme A hydratase 1, and hydroxysteroid (11-beta) dehydrogenase 1. We also determined the subcellular localizations of these enzymes within the mitochondria using immunohistocytochemistry. We believe that these well-characterized antibodies will provide a valuable resource for the Human Liver Proteome Project (HLPP), and will make studies aimed at investigating liver mitochondrial function far easier to perform in future. Our results provide strong evidence that, (i) depletion of dominant proteins from liver mitochondrial samples is possible and, (ii) the approaches adopted in this study can be used to explore or validate protein-protein interactions in this important organelle.
基金supported by the National Basic Research Program of China(Grant Nos.2011CB910601,2011CB910700,2010CB912700 and 2011CB505304)the National High Technology Research and Development Program of China (Grant No.2006AA02A308)+4 种基金National Natural Science Foundation of China(Grant Nos.30700356,30700988,30972909,81000192,81001470 and 81010064)Chinese State Key Project Specialized for Infectious Diseases (Grant Nos.2008ZX10002-016 and 2009ZX10004-103)the National Key Technologies R&D Program for New Drugs (Grant No.2009ZX09301-002)the International Scientific Collaboration Program (Grant Nos.2009DFB33070 and 2010DFA31260)State Key Laboratory of Proteomics(Grant Nos.SKLP-Y200901 and SKLP-O200901)
文摘A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease,treatment decisions,and assessing drug efficacy.This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging.Pooled plasma from different liver fibrosis stages,which were assessed in advance by the current gold-standard of liver biopsy,was quantitatively analyzed.A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process,and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis.Validation results of fibronectin by Western blotting reconfirmed the mass-based data.Ingenuity Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B patients.Consequently,quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver fibrosis.We quantitatively monitored the fibrogenesis process in CHB patients.We discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis disease.These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.
基金supported by the National Natural Science Foundation of China (31100554, 30800177)the National Basic Research Program of China (2007CB914601, 2011CB910802)
文摘The tumor suppressor p53 locates at the key point of cell growth or apoptosis balance, and the expression level of p53 is tightly controlled by ubiquitin ligases including MDM2. Upon DNA damage stresses, p53 was accumulated and activated, leading to cell cycle arrest or apoptosis. We previously showed that Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by interacting with and stabilizing MDM2, and consequently enhancing MDM2-mediated ubiquitylation of p53. However, it is unclear how the Smurf1-MDM2 interaction is regulated in response to DNA damage stress. Here, we show that in response to etoposide treatment Smurf1 dissociates from MDM2, resulting in MDM2 destabilization and p53 accumulation. The negative regulation of Smurf1 on apoptosis is released. Notably, this dissociation is a slow process rather than a rapid response, implicating high expression of Smurf1 might confer the resistance against p53 activation. Consistent with this notion, we observed that Smurf1/2 ligases are highly expressed in colon cancer, esophageal squamous cell carcinoma and pancreatic cancer tissues, suggesting the oncogenic tendency of Smurf1/2.
基金supported by the National Basic Research Program of China (Grant Nos. 2010CB912700 and 2011CB910601)
文摘Functional proteomics can be defined as a strategy to couple proteomic information with biochemical and physiological analyses with the aim of understanding better the functions of proteins in normal and diseased organs.In recent years,a variety of publicly available bioinformatics databases have been developed to support protein-related information management and biological knowledge discovery.In addition to being used to annotate the proteome,these resources also offer the opportunity to develop global approaches to the study of the functional role of proteins both in health and disease.Here,we present a comprehensive review of the major human protein bioinformatics databases.We conclude this review by discussing a few examples that illustrate the importance of these databases in functional proteomics research.
文摘Proteomics is a new science that focuses on the comprehensive analysis of proteins in intact organisms or in molecule machineries, organelles, cells, tissues, or organs. It has become an important area of interests in life sciences and has propelled the rapid development of cutting-edge biotechnology in
基金supported by the National High Technology Research and Development Program of China(2012AA020201)National Basic Research Program of China(2013CB910802,2010CB912700)+2 种基金International Science&Technology Cooperation Program of China(2014DFB30020)National Natural Science Foundation of China(31000379,31000587,31000591)Chinese State Key Project Specialized for Infectious Diseases(2012ZX10002012-006)
文摘Integration of pathway and protein-protein interaction(PPI) data can provide more information that could lead to new biological insights. PPIs are usually represented by a simple binary model, whereas pathways are represented by more complicated models. We developed a series of rules for transforming protein interactions from pathway to binary model, and the protein interactions from seven pathway databases, including PID, Bio Carta, Reactome, Net Path, INOH, SPIKE and KEGG, were transformed based on these rules. These pathway-derived binary protein interactions were integrated with PPIs from other five PPI databases including HPRD, Int Act, Bio GRID, MINT and DIP, to develop integrated dataset(named Path PPI). More detailed interaction type and modification information on protein interactions can be preserved in Path PPI than other existing datasets. Comparison analysis results indicate that most of the interaction overlaps values(OAB) among these pathway databases were less than 5%, and these databases must be used conjunctively. The Path PPI data was provided at http://proteomeview. hupo.org.cn/Path PPI/Path PPI.html.
基金in part by the NationalNatural Science Foundation of China (Grant Nos. 39730310 and 39980007).
文摘The molecular evolutionary tree, also known as a phylogenetic tree, of the serine proteinase superfamily was constructed by means of structural alignment. Three-dimensional structures of proteins were aligned by the SSAP program of Orengo and Taylor to obtain evolutionary distances. The resulting evolutionary tree provides a topology graph that can reflect the evolution of structure and function of homology proteinase. Moreover, study on evolution of the serine proteinase superfamily can lead to better understanding of the relationship and evolutionary difference among proteins of the superfamily, and is of significance to protein engineering, molecular design and protein structure prediction. Structure alignment is one of the useful methods of research on molecular evolution of protein.
文摘The Chinese Academy of Sciences held its 7th forum on frontiers of Science and Technology,April 12-13,2012,in the academy hall of the Chinese Academy of Sciences.The Forum was organized by the Life Science and Medicine Division and co-organized by Academy of Military Medical Sciences and Science China Press.The theme of the 7th Forum was "Lifeomics and Translational Medicine",and the purpose was to discuss the significance of lifeomics(i.e.,
基金the National High Technology Research and Development Program of China (Grant Nos. 2006AA02A312, 2006AA02Z334)National Basic Research Program of China (Grant No. 2006CB910803, 2006CB910706)+1 种基金National Natural Science Foundation of China (Grant No. 30621063)Beijing Municipal Key Project (Grant No. H030330280590)
文摘With the developments of international human transcriptome data and our ESTs of human fetal liver aged 22 weeks (wk) of gestation (HFL22w), the former research must be renewed. In this work, the EST data were firstly clustered by blasting against the ESTs of HFL22w, UniGene, DoTS, MGC and Twinscan-predicted human transcriptome. Then, after EST assembly and gene identification, the known genes were classified by GO (gene ontology), and the unknown genes were predicted by Pfam and ScanProsite to clarify their functions. In the end, the relations of 5 tissues including fetal liver, adult liver, bone marrow, thymus and lymph node that possess hemopoiesis or can indicate fetal liver characteristics were analyzed by hierarchical clustering. The results show that: (i) By comparing the 5 newest human transcriptome databases, we can largely reduce the probability that the ESTs belonging to unconnected parts of one gene were probably divided into different clusters, so it is recommended to blast against the newest databases when clustering EST data; (ii) some previous unknown ESTs had been identified as function-known genes, and 1379 genes were identified as fully new sequences possessed in our lab; (iii) through GO classification, we got a rough understanding of HFL22w, and obtained 6 cell migration genes and 6 hemopoiesis genes; (iv) prediction of gene function had enabled us to obtain 277 profiles, among them, there are 5 categories distributed in more than 10 genes; (v) five tissue relations analyzed by hierarchical clustering are related to their functions; (vi) We have built the world's largest EST database on HFL22w. Renewal and preliminary analysis of EST database on HFL22w will help to understand hemopoiesis and cell migration mechanism, and promote future research on human fetal liver.
