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Randomization of protein encoding gene during species evolution

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Chinese Science Bulletin 1998年第4期43卷 299-303页

作者： GE Weiwen 1 and HE Fuchu 2.1. institute of Hygiene and Environment medicine, Tianjin 300050, china 2. institute of {2. medicine, beijing 100850, china institute of Hygiene and Environment medicine Tianjin China institute of radiation medicine Beijing China

Employing chi_square test, the authors observed the bias of 4 kinds of bases’ locating in 3 codon positions in gene sequence, and proved that there is a positive correlation between higher chi_square value and protein coding structure. By this, the observation that genes undergo progressive reduction in chi_values along evolution direction will reflect the progressive randomization of gene structures and the loss of the characteristics of protein coding sequences. The result proposed that during the evolution of life, genes are unexpectedly degenerating.

关键词： chi_square test gene sequence randomization evolution.

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 {2., beijing 100850, china 2. Department of Life Science, Shandong University, Ji’nan 2.0100, china Correspondence should he addressed to He Fuchu beijing institute of radiation {2. 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.

Effect of wortmannin and 3-AB on G_2.phase arrest and transient failure to activate MPF induced by ionizing irradiation

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Chinese Science Bulletin 1998年第18期43卷 1550-1555页

作者： MENG Xiangbing and SUN Zhixian beijing institute of radiation {2., beijing 100850, china beijing institute of radiation {2. Beijing China

Active mitosis promoting factor (MPF) composed of p34 cdc2.with cyclin B1 is required for the cell cycle transition from G 2.to M phase. Recent studies have demonstrated that ionizing radiation (iR) exposures associated with inhibition of p34 cdc2.activity was the mechanism of G 2.arrest. At low dose, iR causes transient failure to dephosphorylate p34 cdc2.instead of suppression of cyclin B or MPF formation of cyclin B with p34 cdc2.complex. But the signaling events that regulate p34 cdc2.in irradiated cells remain unclear. This note demonstrates that Pi3 kinase family inhibitor wortmannin (wort) and PARP specific inhibitor 3_AB can reduce the G 2.arrest induced by 2.y γ_ray. immunoprecipitation studies demonstrate that wort and 3_AB can facilitate dephosphorylation of p34 cdc2.in G 2.phase arrest induced by radiation. These findings suggest that wort sensitive pathway and PARP may be involved in initiating the signal transduction of G 2.phase arrest caused by iR.

关键词： G 2 phase arrest ionizing radiation MPF wortmannin 3_AB.

Protein Product Encoded by a Human Novel Gene E9730 Enhances AP-1 Activity through interacting with Jab1

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Acta Biochimica et Biophysica Sinica 2004年第1期36卷 11-15页

作者： Zhao-Qing WANG, Han-Dong WEi, and Fu-Chu HE(Department of System Biology, beijing institute of radiation {2., Chinese Human National Center at beijing, beijing 100850, china) Department of System Biology Beijing Institute of Radiation Medicine Chinese Human National Center at Beijing Beijing 100850 China

A novel human gene, named E9730 (a clone number of fetal liver cDNA library), has been identified from more than 14,000 expressed sequence tags (ESTs) based on our large scale sequencing of human fetal liver cDNA libraries. Although sequencing of this novel human gene indicates that it is a leucine zipper protein, the function of E9730 and its homologous genes among species is unknown yet. To find out physiological functional clue of E9730, the yeast two-hybrid system was used to screen the E9730-interac-ting protein(s), and one clone containing a cDNA insert with almost the entire coding sequence (amino acids 39-335) of human Jabl (Jun-activating domain binding protein 1) that interacted specifically with E9730 was identified. A specific association between Jabl and E9730 was shown by co-immunoprecipitation and co-localization experiments. Furthermore, E9730 appeared to enhance Jab 1 -induced AP-1 activity in a concentration-dependent manner and Jabl may be involved in the intracellular signaling trans

关键词： human E9730 gene CSN5/Jabl protein-protein interaction signaling transduction

Explanation of the mechanism of carcinogenesis and syntheses of anticancer agents with high selectivity

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Science china Chemistry 2006年第1期49卷 44-62页

作者： DAi Qianhuan1,2.1. Center of Chemistry and Bioengineering of Cancer Research, beijing Polytechnic University (Now known as beijing Univer-sity of Technology), beijing 10002., china 2. Center of Environmental Sciences, Peking University, beijing 100871, china 1. Center of Chemistry and Bioengineering of Cancer Research Beijing Polytechnic University Beijing 100022 China 2. Center of Environmental Sciences Peking University Beijing 100871 China

in 1979, the mechanism of chemical carcinogenesis, a challenging anddifficult scientific problem pending for a number of years, was explained by Dai Qianhuan. Themechanism named di-region theory predicted that a carcinogen always metabolizes to form a specialbi-functional alky-lating agent. This agent induces cross-linkages between the complementary basepairs in DMA and switches on initial mutageneses in genomes including point and frameshiftmutations. This, in turn, induces further deep mutageneses including the production of variouschimeric chromosomes, deletions and other aberrations found in genomes. in the end this initiatescarcinogenesis of the whole cell through the reverse transcription mechanism after a lengthyincubation period. Recently, this laboratory has verified that physical carcinogenesis, includingthe oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced byendogenous factors such as estrogen or diethyl-stilbestrol switch on carcinogenesis by inducing theformation of cross-linkages between the complementary base pairs in DNA. Di-region theory has nowbeen supported by many experimental observations such as mutational spectra of various *** potential for carcinogenesis, teratogenesis, sterility and mutagenesis lumped together asgenetic toxicity appears to originate almost uniformly from the cross-linking between complementarybases, i.e. malignant cross-linking, which is in accordance with di-region theory. Other forms ofcross-linking between non-complementary bases, benign cross-linkings, show bi-functional alkylationanticancer activity but lack genetic toxicity. The predictable design and synthesis of a highselectivity anticancer agent with high efficacy and low genetic toxicity, a goal long pursued incancer chemotherapy, have been realized for the first time in this laboratory by inhibitingmalignant and heightening benign cross-linking using the principles of di-region theory. A series ofpatented new anticanc

关键词： mechanism of carcinogenesis, di-region theory, minoplatin, selectivity of anticancer agent, cross-linking between DNA bases, anticancer platinum complexes, predictive design of anticancer agent, second generation anticancer agent.

Detection and quantitation of PS2., a phosphorothioate oligodeoxynucleotides in monkey plasma

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Acta Pharmacologica Sinica 2004年第6期25卷 99-104页

作者： Ming-mei SHANG, Hai-feng SONG2. Xiu-wen LiU, Zhong-ming TANG Department of Pharmacology and Toxicology, the institute of radiation medicine, Academy of Military Medical Sciences,{2., china Department of Pharmacology and Toxicology the Institute of Radiation Medicine Academy of Military Medical Sciences

AiM: To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma. METHODS: Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2.00 Da-cutoff membrane. The concentration of the tested S-ODNs, PS2., and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (iS). RESULTS: The method was with good base number specificity. Relative standard deviation % of both intra and inter assay were all less than 10 %, and the total mean recovery was about 91 %. The methodology was successfully used to determine the PK behavior of an anti-tumor antisense S-ODNs in monkeys and identify the metabolites with single base difference. CONCLUSiON: The combined method of solid-phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs, and the main parameters of the methodology met the requirement of PK study.

关键词： antisense oligodeoxyribonucleotides thionucleotides rhesus monkey plasma solid-phase extraction capillary electrophoresis non-gel sieving internal standard

DNA Damage, Signaling and Repair: Protecting genomic integrity and reducing the risk of human disease

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Chinese Science Bulletin 2011年第30期56卷 3119-3121页

作者： ZHOU PingKun Department of radiation Toxicology and Oncology, beijing institute of radiation medicine, beijing 100850, china Special Topic Editor Department of radiation Toxicology and Oncology Beijing Institute of Radiation Medicine

DNA is the genetic material that contains the 'instructions' to not only guide the continuation of life but also govern the development, metabolism and functioning of living organisms. DNA damage occurs daily due to v... 详细信息

关键词： DNA损伤基因组伤信号人类疾病整性修复风险保护

Design and screening of antisense oligodeoxynucleotides against PAi-1 mRNA in endothelial cells in vitro

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Acta Pharmacologica Sinica 2006年第8期27卷 1018-1023页

作者： Qi-sheng JiANG Sheng-qi WANG~2.beijing institute of radiation {2.,beijing 100850,china beijing institute of radiation {2. Beijing 100850 China

Aim:To design and screen antisense oligodeoxynucleotides(ASODNs),whichinhibit type-1 plasminogen activator inhibitor(PAi-1)expression in human umbili-cal vein endothelial cells(HUVEC)in ***:Twenty seven ASODNsagainst different sites of PAi-1 mRNA were designed and transfected to HUVECby lipofectin in *** effects of ASODNs on PAi-1 antigen,PAi-1 activityand PAi-1 mRNA expression were detected by ELiSA,amidolytical assay and RT-PCR,***:Transforming growth factor β1(TGF-β1)-treatedHUVEC increased the expression of PAi-1 compared with the normal *** among twenty seven designed ASODNs were effective in inhibiting the in-crease in PAi-1 antigen and PAi-1 activity in a dose-dependent manner after *** particular,ASODN 14(AO14)exhibited the best inhibitory *** control sequences of AO14,including sense,scramble,and mismatchsequences,did not significantly inhibit PAi-1 *** was revealed that theinhibitory efficacy of AO14 was in a sequence-specific ***-PCR showedthat ASODN 1,7,8,14,and 15 decreased PAi-1 mRNA expression induced byTGF-β1and AO14 showed the best inhibitory ***:ASODN 1,7,8,14,and 15,among twenty seven designed ASODNs against PAi-1 mRNA,signifi-cantly decreased PAi-1 antigen and PAi-1 activity induced by TGF-β1x in a dose-dependent manner in HUVEC in ***14 showed the best inhibitory effect onPAl-1 expression in a sequence-specific *** results of RT-PCR indicatedthat inhibitory effects of ASODNs on PAi-1 biosynthesis occurred at the *** among five effective target sites of ASODNs located at the translationinitiation Site or within the translation area of PAi-1 mRNA,suggesting that thesesites may be promising sites for the design of effective ASODNs.

关键词： plasminogen activator inhibitor 1 antisense oligodeoxynucleotide endothelial cells

A Putative NES Mediates Cytoplasmic Localization of Apoptin in Normal Cells

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Acta Biochimica et Biophysica Sinica 2004年第12期36卷 817-823页

作者： Qing-Ming WANG*, Guo-Cai FAN, Ji-Zhong CHEN, Hui-Peng CHEN, and Fu-Chu HE* Department of Genomics and Proteomics, beijing institute of radiation {2., beijing 100850, china Department of Genomics and Proteomics Beijing Institute of Radiation MedicineBeijing 100850 China

Apoptin, a protein expressed by chicken anemia virus, is found predominantly in the cytoplasm in normal cells, whereas it localizes in the nucleus in transformed and malignant cells. However, the mecha- nisms that regulate the different subcellular localization of Apoptin in normal and tumor cells have not been fully clarified. in this work, a putative nuclear export signal (NES) in Apoptin was predicted. it was testified that the putative NES (pNES) of Apoptin was not a functional NES, but actually acted as a cytoplasmic retention signal. Deletion of the pNES led to the nuclear accumulation of Apoptin in normal cells. in addition, when a strong nuclear localization signal was introduced into Apoptin, it exclusively translocated to the nucleus in normal cells. These observations indicated that the cytoplasmic localization of Apoptin in normal cells results from the balance between cytoplasmic retention and nuclear import. On the other hand, the pNES was also proved to be necessary for Apoptin multimerization. Mutants lacking the pNES did not form obviously visible globular aggregates in normal or tumor cells.

关键词： Apoptin nuclear localization signal cytoplasmic retention signal nuclear export signal