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| 1 | Neddylation of PTEN regulates its nuclear import and promotes tumor development显示文摘PTEN tumor suppressor opposes the PI3K/Akt signaling pathway in the cytoplasm and maintains chromosomal integrity in the nucleus.Nucleus–cytoplasm shuttling of PTEN is regulated by ubiquitylation,SUMOylation and phosphorylation,and nuclear PTEN has been proposed to exhibit tumor-suppressive functions.Here we show that PTEN is conjugated by Nedd8 under high glucose conditions,which induces PTEN nuclear import without effects on PTEN stability.PTEN neddylation is promoted by the XIAP ligase and removed by the NEDP1 deneddylase.We identify Lys197 and Lys402 as major neddylation sites on PTEN.Neddylated PTEN accumulates predominantly in the nucleus and promotes rather than suppresses cell proliferation and metabolism.The nuclear neddylated PTEN dephosphorylates the fatty acid synthase(FASN)protein,inhibits the TRIM21-mediated ubiquitylation and degradation of FASN,and then promotes de novo fatty acid synthesis.In human breast cancer tissues,neddylated PTEN correlates with tumor progression and poor prognosis.Therefore,we demonstrate a previously unidentified pool of nuclear PTEN in the Nedd8-conjugated form and an unexpected tumor-promoting role of neddylated PTEN. | Ping Xie Zhiqiang Peng Yujiao Chen Hongchang Li Mengge Du Yawen Tan Xin Zhang Zhe Lu Chun-Ping Cui Cui Hua Liu Fuchu He Lingqiang Zhang | 2021 | Cell Research2021，31，3： | 11 |
| 2 | Lifeomics leads the age of grand discoveries显示文摘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. | HE FuChu | 2013 | Science China(Life Sciences)2013，56，3： | 8 |
| 3 | LSECtin on tumor-associated macrophages enhances breast cancer sternness via interaction with its receptor BTN3A3显示文摘Macrophages have bee n suggested to con tribute to con structing a cancer stem cell(CSC)niche.However,whether and how macrophages regulate the activity of CSCs through juxtacrine signaling are poorly understood.Here we report LSECtin,a transmembrane protein highly expressed on tumor-associated macrophages(TAMs),enhances sternness of breast cancer cells(BCCs).We identified BTN3A3,a B7 family member with previously unknown functions as the receptor for LSECtin on BCCs responsible for stemness-promoting effect of LSECtin.In mice bearing human tumor xenografts,either macrophage-specific ablation of LSECtin or silencing of BTN3A3 in BCCs decreased CSC frequency and tumor growth.Admixture of LSECtin-positive macrophages increased the tumorigenic activity of BCCs dependent on BTN3A3.Disruption of the LSECtin-BTN3A3 axis with BTN3A3-Fc or anti-BTN3A3 mAb has a therapeutic effect on breast cancer.These findings define a juxtacrine signaling mechanism by which TAMs promote cancer stemness.Targeting this axis in the CSC niche may provide potential therapies to breast cancer. | Di Liu Qian Lu Xing Wang Jun Wang Ning Lu Zefei Jiang Xiaopeng Hao Jianbin Li Jing Liu Pengbo Cao Guilin Peng Yuandong Tao Dianyuan Zhao Fuchu He Li Tang | 2019 | Cell Research2019，29，5： | 8 |
| 4 | CKIP-1 regulates macrophage proliferation by inhibiting TRAF6-mediated Akt activation显示文摘巨噬细胞在开发,动态平衡,织物修理和免疫起枢轴的作用。巨噬细胞增长被刺激殖民地的因素(M-CSF ) 导致了 Akt 发信号的巨噬细胞支持;然而,这个过程怎么被终止,仍然保持不清楚。这里,我们作为巨噬细胞增长的一个新奇禁止者识别酷蛋白 kinase 2-interacting protein-1 (CKIP-1 ) 。在放松巨噬细胞, CKIP-1 是在由组成地活跃的 GSK3β 的丝氨酸 342 点的 phosphorylated;, Akt 的下游的目标。这 phosphorylation 触发 CKIP-1 的 polyubiquitination 和 proteasomal 降级。在 M-CSF 刺激之上, Akt 被 CSF-1R-PI3K 激活然后使 GSK3β 失去活性;,导致 CKIP-1 和 β 的稳定; -catenin 蛋白质。β -catenin 包括 cyclin D 和 c-Myc 支持增长基因的表示。CKIP-1 与 TRAF6,为连接 K63 的 ubiquitination 要求的 ubiquitin ligase 和 Akt 的血浆膜招募交往,并且终止调停 TRAF6 的 Akt 激活。由这个工具, CKIP-1 在 M-CSF 刺激以后在迟了的阶段明确地禁止巨噬细胞增长。而且, CKIP-1 缺乏在老鼠自发地开发的 vitro 和 CKIP-1 −/− 导致增加的增长和巨噬细胞的减少的 apoptosis 巨噬细胞主导的脾大和 myeloproliferation。一起,这些数据证明 CKIP-1 由禁止调停 TRAF6 的 Akt 激活在巨噬细胞动态平衡的规定起一个关键作用。 | Luo Zhang Yiwu Wang Fengjun Xiao Shaoxia Wang Guichun Xing Yang Li Xiushan Yin Kefeng Lu Rongfei Wei Jiao Fan Yuhan Chen Tao Li Ping Xie Lin Yuan Lei Song Lanzhi Ma Lujing Ding Fuchu He Lingqiang Zhang | 2014 | Cell Research2014，24，6： | 7 |
| 5 | Nusap1 is essential for neural crest cell migration in zebrafish显示文摘Microtubules play important roles in mitotic spindle assembly and chromosome segregation to maintain normal cell cycle progression.A number of microtubule-associated proteins have been identified in epithelial and neural cell cultures;however,their physiological significance is not well characterized due to the lack of appropriate in vivo animal models.Nucleolar spindleassociated protein(NuSAP)is a microtubule-binding protein and is reported to be involved in mitosis by cell culture studies.In this report,we identified the zebrafish homologue of human NuSAP and investigated its expression profile and functions.Using in situ hybridization,we demonstrated that transcripts of zebrafish nusap1 are specifically expressed in the retina,forebrain,hindbrain and neural crest.When the in vivo expression of nusap1 was knocked down through antisense oligonucleotide morpholino technology,the morphants of nusap1 showed impaired morphogenesis in the trunk and yolk extension,implying the involvement of Nusap1 in cell migration.Mechanistic studies revealed that nusap1 morphants have an altered expression pattern of neural crest markers crestin and sox9b,but normal expression of blood vessel and notochord markers gata1 and shh.In addition,nusap1 mRNA injection caused serious apoptosis in retina and hindbrain tissue,and these phenotypes can be rescued by co-injection of morpholino against nusap1.These observations not only suggest a role for Nusap1 in connecting apoptosis with cell migration,but also provide strong evidences that Nusap1 is potentially involved in morphogenesis in vertebrates. | Jing Nie Hua Wang Fuchu He Huizhe Huang | 2010 | Protein & Cell2010，1，3： | 7 |
| 6 | At a glance:Proteomics in China显示文摘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 | HE FuChu | 2011 | Science China(Life Sciences)2011，54，1： | 6 |
| 7 | Antigenically dominant proteins within the human liver mitochondrial proteome identified by monoclonal antibodies显示文摘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. | JU YanFang YANG JinJu LIU Rong LIU XiaoLan DU XueMei LIU Li CHEN ZhiCheng CHI Jun LIU ShuEr GAO Yuan GAO JianEn JIAO ShunChang HE FuChu SUN QiHong | 2011 | Science China(Life Sciences)2011，54，1： | 6 |
| 8 | Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy显示文摘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. | LI ShuLong LIU Xin WEI Lai WANG HuiFen ZHANG JiYang WEI HanDong QIAN XiaoHong JIANG Ying HE FuChu | 2011 | Science China(Life Sciences)2011，54，5： | 6 |
| 9 | Applications of proteomics in hepatic diseases research显示文摘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. | SUN Wei HE Fuchu | 2004 | Science China(Life Sciences)2004，47，2： | 4 |
| 10 | CKIP-1 suppresses the adipogenesis of mesenchymal stem cells by enhancing HDACl-associated repression of C/EBPα显示文摘 | Dahu Li HengZhu Chao Liang Wenbo Li Guichun Xing Lanzhi Ma Lujing Ding Yi Zhang Fuchu He Lingqiang Zhang | 2014 | Journal of Molecular Cell Biology2014，8，5： | 4 |
| 11 | Human hepatopoietin augmenter of liver regeneration──A hepatotrophic factor for liver regeneration, and its potential antihepatitis effect in vivo显示文摘The effect of human hapatopoietin i.e. augmenter of liver regeneration (hALR) was determined on hepatocyte DNA synthesis, and on CCl 4-induced hepatitis in animal in vitro and in vivo. It is found that ALR could directly stimulate DNA synthesis of hepatocytes in primary culture in a dose-dependent manner. In 30% hepatectomied rats, significant DNA synthesis occurred in control rats ; even so, exogenous hALR gene encoding protein increased DNA synthesis of regeneration liver by 2.3 fold compared with control rats. A lower dose of CCl 4 was administrated in rats and the effect of ALR on DNA synthesis of regenerating liver 48 h after CCl 4 administration was analyzed. Few Budr-labeled hepatocytes were visible in control rats. However, exogenous hALR markedly increased the number of labeled cells in a dose-dependent manner. Statistical analysis showed that 10 or 40 μg·kg -1 ALR protein stimulated DNA synthesis by 1.7 and 4.8 fold respectively. In addition to enhancing cell growth, adiministration of hALR achieved a significant improvement in reversing the lethality of rat hepatic failure when compared with that of control group; the elevation of cytosolic enzymes was dramatically suppressed by exogenous hALR in CCl 4-treated mice in vivo and in vitro; histologically, hepatocytes around the central vein were necrotic, and the degree of hepatocyte necrosis in control mice was more prominent than that in the mice given 40 μg·kg-1 hALR 48 h after CCl 4 administration. We also noted that hALR had a strong antihepatitis effect in vitro which was determined with primary cultured rat hepatocytes. These findings suggest that hALR protects the integrity of hepatocytes against severe hepatitis, and indicate that ALR may be an important regulator of liver regeneration and play a major role in liver injury repair. It proves ALR adminstration to be a useful treatment to accelerate liver regeneration and to prevent the onset of hepatitis or intrahepatic cholestasis induced by toxin. | YANG Xiaoming 1, WANG Aimin 2, ZHOU Ping 3, XIE Ling 1, WANG Qingming 1, WU Zuze 1 and HE Fuchu 1 1. Institute of Radiation Medicine, Beijing 100850, China 2. No. 252 Hospital of PLA, Baoding 071000, China 3. General Hospital of the Air | 1998 | Chinese Science Bulletin1998，43，12： | 3 |
| 12 | An overview of human protein databases and their application to functional proteomics in health and disease显示文摘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. | ZHANG YanQiong ZHU YunPing HE FuChu | 2011 | Science China(Life Sciences)2011，54，11： | 2 |
| 13 | DNA damage stress induces the dissociation of Smurf1/2 from MDM2 in a slow manner显示文摘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. | NIE Jing LIU Lin ZHAO XiaoHang XIE Ping ZHOU PingKun XING GuiChun LIU XiangJun HE FuChu HAN WeiDong ZHANG LingQiang | 2011 | Chinese Science Bulletin2011，56，30： | 2 |
| 14 | Path PPI: an integrated dataset of human pathways and protein-protein interactions显示文摘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. | TANG HaiLin ZHONG Fan LIU Wei HE FuChu XIE HongWei | 2015 | Science China(Life Sciences)2015，58，6： | 2 |
| 15 | An integrated view of the correlations between genomic and phenomic variables显示文摘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. | Dong Yang,Ying Jiang,Fuchu He State Key Laboratory of Proteomics,Beijing Proteome Research Center,Beijing Institute of Radiation Medicine,Beijing 102206,China | 2009 | Journal of Genetics and Genomics2009，36，11： | 2 |
| 16 | Properties and applications of embryonic stem cells显示文摘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. | 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 | 2000 | Chinese Science Bulletin2000，45，14： | 2 |
| 17 | Progress in study of structure-function relationship and protein engineering of plasminogen activators显示文摘Thrombolytic agents play an important role in the treatment of thrombus diseases. In clinic,traditional thrombolytic agents always resulted in the side effect of systemic thrombolysis because of the shortcomings, such as short half-life, poor specificity of thrombus. Recently, with the development of knowledge of the relationship between their structure and function, a series of new thrombolytic agents were constructed by means of molecular biological techniques. Developing new types of thrombolytic agents is of great significance for more effective treatment of cardiovascular diseases. The latest knowledge of the structure-function relationship of t-PA and u-PA and the progress in development of new thrombolytic agents are reviewed. | Fuxiang Zhu Fuchu He | 1999 | Chinese Science Bulletin1999，44，4： | 2 |
| 18 | C-type lectin LSECtin interacts with DC- SIGNR and is involved in hepatitis C virus binding 显示文摘 | Li Yi He Fuchu | 2009 | Mol Cell Biochem2009，327，： | 1 |
| 19 | Differential regulation of Apak by various DNA damage signals显示文摘 | Shan Wang Chunyan Tian Tingtiang Xiao Guichun Xing Fuchu He Lingqiang Zhang Hong Chen | 2010 | Molecular and Cellular Biochemistry (-)2010，，1： | 1 |
| 20 | A Yeast BiFC-seq Method for Genome-wide Interactome Mapping显示文摘Genome-wide physical protein±protein interaction(PPI)mapping remains a major challenge for current technologies.Here,we reported a high-efficiency BiFC-seq method,yeastenhanced green fluorescent protein-based bimolecular fluorescence complementation(y EGFPBiFC)coupled with next-generation DNA sequencing,for interactome mapping.We first applied y EGFP-BiFC method to systematically investigate an intraviral network of the Ebola virus.Two-thirds(9/14)of known interactions of EBOV were recaptured,and five novel interactions were discovered.Next,we used the BiFC-seq method to map the interactome of the tumor protein p53.We identified 97 interactors of p53,more than three-quarters of which were novel.Furthermore,in a more complex background,we screened potential interactors by pooling two BiFC libraries together and revealed a network of 229 interactions among 205 proteins.These results show that BiFC-seq is a highly sensitive,rapid,and economical method for genome-wide interactome mapping. | Limin Shang Yuehui Zhang Yuchen Liu Chaozhi Jin Yanzhi Yuan Chunyan Tian Ming Ni Xiaochen Bo Li Zhang Dong Li Fuchu He Jian Wang | 2022 | Genomics, Proteomics & Bioinformatics2022，20，4： | 1 |
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