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Renewal and preliminary study of expressed sequence tags database on human fetal liver aged 22 wk of gestation

Chinese Science Bulletin 2008年第20期53卷 3204-3210页

作者： CheN TingGui WU SongFeng ZHOU GangQiao ZHU YunPing he fuchu State Key Laboratory of Proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Beijing 102206 China Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Shanxi University Taiyuan 030006 China

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.

关键词：怀孕期胎儿肝脏表达序列基因存在论分级聚类

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Properties and applications of embryonic stem cells

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Chinese Science Bulletin 2000年第14期45卷 1258-1265页

作者： GUO Xiaoxia & he fuchu1. Beijing Institute of Radiation Medicine, Beijing 100850, China 2. Department of Life Science, Shandong University, Ji’nan 250100, China Correspondence should he addressed to he fuchu Beijing Institute of Radiation Medicine Beijing China Department of Life Science Shandong University Ji’nan China

Mouse embryonic stem (ES) cells are pluripotent cells derived from the early embryo and can be propagated stably in undifferentiated state in vitro. They retain the ability to differentiate into all cell types found in the embryonic and adult body in vivo, and can be induced to differentiate into many cell types under appropriate culture conditions in vitro. Using these properties, people have set up various differentiated systems of many cell types and tissues in vitro. Through analysis of these systems, one can identify novel bioactive factors and reveal mechanisms of cell differentiation and organogenesis. ES cell-derived differentiated cells can also be applied to cell transplantation therapy. In addition, we summarized the features and potential applications of human ES cells.

关键词： embryonic stem cell differentiation in vitro cell transplantation therapy gene targeting.

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A new method of research on molecular evolution of proteinase superfamily

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Chinese Science Bulletin 2001年第7期46卷 578-582页

作者： SUN Zhirong JI Xinglai HU Shengmin WANG Yu he fuchu Department of Biology Tsinghua UniversityBeijing 100084China Radiate Medicine Institute Academy of Military Medical SciencesBeijing 100850China

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.

关键词： molecular evolution SSAP algorithm structure alignment evolutionary tree serine proteinase superfamily.

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Exploration of Target Spaces in the Human Genome for Protein and Peptide Drugs

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Genomics, Proteomics & Bioinformatics 2022年第4期20卷 780-794页

作者： Zhongyang Liu Honglei Li Zhaoyu Jin Yang Li Feifei Guo Yangzhige he Xinyue Liu Yaning Qi Liying Yuan fuchu he Dong Li State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China College of Chemistry and Environmental Science Hebei UniversityBaoding 071002China Suzhou Geneworks Technology Co. Ltd.Suzhou 215028China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Department of Medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China College of Life Sciences Hebei UniversityBaoding 071002China

After decades of development,protein and peptide drugs have now grown into a major drug class in the *** identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target ***,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are ***,we systematically explore the target spaces in the human genome specifically for protein and peptide *** with other proteins,both successful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many *** on these features,we develop separate effective genome-wide target prediction models for protein and peptide ***,a user-friendly web server,Predictor Of Protein and Pept Ide drugs’therapeutic Targets(POPPIT)(http://***/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.

关键词： Protein drug Peptide drug Target analysis Target prediction Web server

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ARF-mediated SUMOylation of Apak antagonizes ubiquitylation and promotes its nucleolar accumulation to inhibit 47S pre-rRNA synthesis

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分子细胞生物学报:英文版 2015年第2期7卷 154-167页

作者： Shan Wang Siying Wang Lihua Yang Hua Guo Xue Kong Lin Yuan Guichun Xing fuchu he Lingqiang Zhang StateKeyLaboratory of Proteomics Beijing Proteome Research CenterBeijing Institute of Radiation MedicineCollaborative Innovation Center for Cancer MedicineBeijing 100850China Institute of Cancer Stem Cell Dalian Medical UniversityDalian 116044China Department of Biochemistry and Molecular Biology Anhui Medical UniversityHefei 230032China Department of Scientific Research Xiang-Ya HospitalCentral South UniversityChangsha 410008China

Ribosomes are among the most fundamental molecular machines in all cells,as they are required for protein *** structural rRNA components are generated in the nucleolus and assembled into pre-ribosomal *** we show Apak,a previously identified p53 inhibitor,as a novel ribosomal stress response *** unstressed cells,Apak is bound to the deSUMOylase SENP1 in the nucleoplasm and targeted for proteasomal degradation by MDM2 ubiquitin *** ribosomal stress,SENP1 dissociates fromApak and the tumor suppressor protein ARF couplesUbc9 with Apak to promote Apak SUMOylation on zinc *** results in Apak protein stabilization and translocation to the nucleolus,where Apak inhibits the pre-rRNA *** findings provide a molecular mechanism whereby ARF coordinates Apak to regulate ribosome biogenesis upon cellular stress.

关键词： nucleolus nucleolar stress Apak ARF SUMOylation

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Science China Chemistry 2016年第3期59卷 380-382页

作者： Li Feng Hong Li Yang Zhang Huali Shen Hongxiu Yu Fan Zhong Lunxiu Qin fuchu he Pengyuan Yang Zhaoyou Tang Minhang Hospital Fudan UniversityShanghai201199China Department of Chemistry Fudan UniversityShanghai200433China Institutes of Biomedical Sciences Fudan UniversityShanghai200032China Zhongshan Hospital Fudan UniversityShanghai200032China

Recently, we have analyzed expressional transcriptome and proteome for a number of cancer cell lines, including 8 hepatocellular carcinoma （HCC） ones [1,2]. These 8 HCC cell lines consist of 6 metastatic （all with mutant p53） and 2 non-metastatic （with a mutant and a lost p53） ones, being all HBV traceable for relatively close genetic-backgrounds. We have analyzed the related dataset and obtained transcrip- tome （16353 genes） and proteome （7861 proteins） of these 8 HCC cell lines, and explored a group of up-regulated and down-regulated genes [3].

关键词： Cell culture Chromosomes Genes Pathology

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CKIP-1 suppresses the adipogenesis of mesenchymal stem cells by enhancing HDACl-associated repression of C/EBPα

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Journal of Molecular Cell Biology 2014年第5期8卷 368-379页

作者： Dahu Li hengZhu Chao Liang Wenbo Li Guichun Xing Lanzhi Ma Lujing Ding Yi Zhang fuchu he Lingqiang Zhang State Key Laboratory of Proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Collaborative Innovation Center for Cancer Medicine Beijing 100850 China Beijing Institute of Basic Medical Sciences Beijing 100850 China Laboratory Animal Center of the Academy of Military Medical Sciences Beijing 100850 China Institute of Cancer Stem Cell Dalian Medical University Dalian 116044 China

Mesenchymal stem cells （MSCs） are considered as the developmental origin of multiple Uneage cells including osteocytes, adipocytes, and muscle cells. Previous studies demonstrated that the PH *** protein CKIP-1 plays an important role in the devel- opment of osteobiasts and cardiomyocytes. However, whether CKIP-1 is involved in the generation of adipocytes as weU as the MSC differentiation remains unknown. here we show that CKIP-1 is a novel regulator of MSCs differentiating into adipocytes. MSCs derived from CKIP-l-deficient mice display enhanced adipogenesis upon induction. Further analysis showed that CKIP-1 interacts with the histone deacetylase HDAC1 in the nucleus and inhibits the transcription of CCAAT/enhancer-binding protein α （C/EBPcx）, which is a crucial adipogenic transcription factor. Ectopic expression of CKI P-1 in a MSC-Uke cell line C3H/10T1/2 reduced the gener- ation of adipocytes due to suppression of adipogenic factors, including C/EBPα. Moreover, CKI P-l-deficient mice showed an increase in body weight and white adipose tissue gains when fed on a high-fat diet. Collectively, these results suggest that CKIP-1 is a novel inhibitor of MSC-originated adipogenesis by enhancing HDACl-associated repression of C/EBPα.

关键词： adipogenesis mesenchymal stem cells C/EBPa CKIP-1 HDAC1

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An integrated view of the correlations between genomic and phenomic variables

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Journal of Genetics and Genomics 2009年第11期36卷 645-651页

作者： Dong Yang,Ying Jiang,fuchu he State Key Laboratory of Proteomics,Beijing Proteome Research Center,Beijing Institute of Radiation Medicine,Beijing 102206,China State Key Laboratory of Proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Beijing 102206 China

Genome sequencing opened the flood gate of ＂-omics＂ studies, among which the research about correlations between genomic and phenomic variables is an important part. With the development of functional genomics and systems biology, genome-wide investigation of the correlations between many genomic and phenomic variables became possible. In this review, five genomic variables, such as evolution rate （or ＂age＂ of the gene）, the length of intron and ORF （protein length） in one gene, the biases of amino acid composition and codon usage, along with the phenomic variables related to expression patterns （level and breadth） are focused on. In most cases, genes with higher mRNA/protein expression level tend to evolve slowly, have less intronic DNA, code for smaller proteins, and have higher biases of amino acid composition and codon usage. In addition, broadly expressed proteins evolve more slowly and are shorter than tissue-specific proteins. Studies in this field are helpful for deeper understanding the signatures of selection mediated by the features of gene expression and are of great significance to enrich the evolution theory.

关键词： genomic variable phenomic variable expression pattern evolution selection

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Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy

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Science China(Life Sciences) 2011年第5期54卷 393-402页

作者： LI ShuLong LIU Xin WEI Lai WANG HuiFen ZHANG JiYang WEI HanDong QIAN XiaoHong JIANG Ying he fuchu State Key Laboratory of Proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Beijing 102206 China Beijing Institute of Biotechnology Beijing 100071 China People 's Hospital of Peking University Beijing 100044 China 302 Military Hospital of China Beijing 100039 China Institutes of Biomedical Sciences Fudan University Shanghai 200032 China Central Laboratory Yantai Yu-Huang-Ding Hospital Yantai 264000 China

A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease,treatment decisions,and assessing drug *** 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 *** 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 *** results of fibronectin by Western blotting reconfirmed the mass-based *** Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B ***,quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver *** quantitatively monitored the fibrogenesis process in CHB *** discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis *** results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.

关键词： quantitative proteomics fiver fibrosis biomarker plasma hepatitis B virus

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Applications of proteomics in hepatic diseases research

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Science China(Life Sciences) 2004年第2期47卷 101-106页

作者： SUN Wei he fuchu Laboratory of Systems Biology Beijing Institute of Radiation Medicine Beijing 100850 China Laboratory of Systems Biology Beijing Institute of Radiation Medicine Beijing 100850 China

Proteomics has become an important part in the leading research area and been widely used in the disease-associated study. In hepatic research field, proteomics could be ap-plied in study of hepatic diseases including liver cancer, cirrhosis and hepatotoxicities, etc. Sig-nificant proteins could be identified as biomarkers, drug targets and clues for pathogenesis illu-mination.

关键词： proteomics, hepatic diseases.

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