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miRNAs modulate the drug response of tumor cells

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Science china(Life sciences) 2009年第9期52卷 797-801页

作者： wu xuemei1,3.& xiao huasheng1,2.1 Center of Functional Genomics,Key Laboratory of System Biology,{2.,{3.,shanghai 2.003.,china 2.National Engineering Center for Biochip at shanghai,shanghai 2.12.3.china 3.Graduate University of {3.,shanghai 2.003.,china Center of Functional Genomics Key Laboratory of System Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China National Engineering Center for Biochip at shanghai Shanghai 201203 China Graduate University of chinese academy of sciences Shanghai 200031 China

Chemotherapy is one of the major treatments of malignant carcinomas. However,its efficiency is affected by both intrinsic and acquired resistance to anticancer drugs. The cellular mechanisms of drug resistance include the overexpression of energy-dependent transporters that eject anticancer drugs from cells such as p-glycoprotein and multidrug resistance related protein (MRP),the mutation of drug targets,the activation of DNA repair pathways,the defects in cellular death pathways and so on. The genetic and epigenetic changes of these genes can lead to cancer drug resistance. Among these mechanisms,microRNAs (miRNAs) which are critical and essential for many important processes such as development,differentiation,and even carcinogenesis have been reported to regulate the chemosen-sitivity of tumor cells. In this paper we briefly review the relationship between miRNA and cancer drug resistance.

关键词： cancer drug resistance miRNAs

Sequence analysis of mRNA polyadenylation signals of rice genes

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chinese Science Bulletin 2006年第9期51卷 1069-1077页

作者： LU Ying1, 2. GAO Chenxi1,2.3.& HAN Bin1,3.41. National Center for Gene Research, {3., {2., {2. 2.02.3. {3. 2. Graduate School of the {2., Beijing 10003., {3. 3. Institute of Plant Physiology and Ecology, {3., {2., shanghai 2.003., {3. National Center for Gene Research Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200233 China Graduate School of the chinese academy of sciences Beijing 100039 China Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

The formation of eukaryotic mRNAs involves the cleavage and polyadenylation of pre- mRNAs. To investigate the sequence requirement of putative polyadenylation signals (PASs), poly(A) sites and downstream elements (DUEs) in 3.-end-pro- cessing in rice, we compared expressed sequences tags (ESTs) with poly(A) extremity to full-length cDNA sequences and constructed a database of 12.69 pre- mRNA sequences in ?40―+40 nt surrounding the poly(A) sites, which were from 9953.genes. The al- ternative poly(A) sites were revealed in approxi- mately 2.% of mRNAs. Nearly 80% of pre-mRNAs showed stringent requirement of the YA (CA or UA) at poly (A) sites for polyadenylation. About 7.9% had the AAUAAA signals on ?40―?1 nt upstream of the poly(A) sites. Over 60% of mRNAs probably used the one- or two-base variants of AAUAAA hexamers as their PASs in 3. fragments. The single-base variants of AAUGAA revealed the high frequency in 11.5% of 3. fragments. The DUEs were detected in 90% of pre- mRNAs, especially more than half of the pre-mRNAs with multi-base variants of AAUAAA had the DUEs surrounding the poly(A) site. The location of DUE is also important for defining the cleavage site. Al- though most of the rice pre-mRNAs did not contain AAUAAA signal, the existence of downstream ele- ments ensured the efficiency of cleavage-polyade-

关键词：多聚腺苷酸序列分析 mRNA 水稻基因工程

Functional analysis of schistosomes EF-hand domain-containing tegument proteins

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chinese Science Bulletin 2007年第15期52卷 2100-2107页

作者： YU FuDong1,2.3.KANG Bin1,3.LI YuanYuan3.4 & LI YiXue1,3.1 Bioinformatics Center,Key Laboratory of Systems Biology,shanghai institutes for biological sciences,chinese {2. of Sci-ences,{3.,china 2.Graduate University of chinese academy of sciences,{3.,china 3.shanghai Center for Bioinformation Technology,shanghai 2.02.5,china 4 Key Laboratory of Systems Biology,shanghai institutes for biological sciences,chinese academy of sciences,{3.,china Bioinformatics Center Key Laboratory of Systems Biology Shanghai Institutesfor Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Schistosomes cause schistosomiasis disease which severely threatens human health. Little is known about the functions of EF-hand domain containing schistosomes tegument proteins other than as an-tigens. More possible functions of these tegument proteins were investigated with in silico analyses including protein-protein functional interaction,site-specific variation and glycosylation modification. The analysis results suggested that schistosomes could actively modulate host immune responses for its own favor through functional interactions with host proteins with immunomodulatory function,and passively regulate host immune responses through sequence variation under positive selection and glycosylating the recognition sites of host immune attack. In addition,the analysis of the C-terminal domain of these tegument proteins indicated that they could assist schistosomes in escaping host immune attacks through inhibiting chemotaxis and non-complement fixing antibody (IgG4) responses. In summary,our results suggested that these tegument antigen proteins could assist schistosomes in escaping and modulating host immune responses for self-protection during the process of host-para-site interaction.

关键词：寄生虫血吸虫皮蛋白质健康

Axon guidance and neuronal migration research in china

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Science china(Life sciences) 2010年第3期53卷 304-314页

作者： YUAN xiaoBing Institute of Neuroscience,shanghai institutes for biological sciences,{2.,{3.,china 1. Institute of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal *** progress in research of axon guidance and neuronal migration has been made in the last twenty *** researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal *** unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by chinese neuroscientists to investigate the molecular machinery underlying these guidance events.

关键词： axon guidance neuronal migration development neuronal circuits

Association between Alcohol, Smoking and HLA-DQA1*02.1 Genotype in Psoriasis

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Acta Biochimica et Biophysica Sinica 2004年第9期36卷 597-602页

作者： Guang-Yong ZHENG1,2., Sheng-Cai WEI3., Tie-Liu SHI1, and Yi-Xue LI1* 1Bioinformatics Center, shanghai institutes for biological sciences, chinese academy of sciences, Graduate School of the chinese academy of sciences, {3., china Research Center for Proteome Analysis, Institute of Biochemistry and Cell Biology, shanghai institutes for biological sciences, chinese academy of sciences, Graduate School of the chinese academy of sciences, {3., china 3.uangzhou Institute of Dermatology, Guangzhou 510095, china Bioinformatics Center Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences

Psoriasis is a chronic skin disease triggered by genetic, environment or other risk factors such as infection, drugs, stress, moisture, alcohol, and smoking. A major psoriasis susceptibility locus at 6p2..3. has been identified. Further studies found that HLA-DQA1*02.1 allele was associated with psoriasis. However, there were few data exploring an association between the environmental factors and susceptibility genes. In this study, the samples of 189 patients with psoriasis and 3.3.healthy controls were collected with their consent and were carried on analysis through polymerase chain reaction sequence-specific primer (PCR- SSP) method. The proportion of male psoriasis patients engaging in the smoking and alcohol was much higher than that of the control group (P2.1 allele was present at significantly higher frequency in the patients with psoriasis (OR=4.2., P2.1 in male patients with psoriasis (OR>6.91, P<1.0×10–4).

关键词： psoriasis HLA-DQA1*02.1 allele smoking alcohol association

TNF receptor-associated factor-2.binding site is involved in TNFR75-dependent enhancement of TNFR55-induced cell death

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Cell Research 2001年第3期11卷 217-222页

作者： LU FANG, JIA FANG, CHANG QING CHEN shanghai Research Center of Biotechnology, shanghai institutes for biological sciences the {2., shanghai 2.02.3. china 1shanghai Research Center of Biotechnology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200233 China. 1shanghai Research Center of Biotechnology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200233 China. 1shanghai Research Center of Biotechnology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200233 China.

TNF recepter-55 is the main mediator of TNF-induced apoptosis. TNF receptor-75-dependent induction or enhancement of cytotoxicity has been explained by intracellular signaling, 'ligand passing' , or induction of endogenous TNF. To study the function of human TNF receptor-75 (hTR75) and the interaction between human TNF receptor-55 (hTR55) and hTR75 in hTNFa-induced cytotoxicity, HEp-2.cells were transfected with bicistronic expression vector of hTR75 and its deletion mutants genes. hTNFa-induced cytotoxicity was determined by crystal violet colorimetric method. The expression of hTR75 and its deletion mutants in HEp-2.cells was demonstrated by RT-PCR and indirect ELISA. We found that the overexpressed hTR75 could significantly increase the susceptibility of HEp-2.cells to hTNFa which especially required TRAF2.binding site. hTR75 could not only mediate partial hTNFa-induced cytotoxicity independently but also fulfill an accessory role in enhancing or synergizing hTR55-mediated cytotoxicity

关键词： hTNFa hTNF receptors TRAF2 cytotoxcity signal transduction.

The Role of Propeptide in the Refolding of Human Group IB Phospholipase A2

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Acta Biochimica et Biophysica Sinica 2004年第9期36卷 583-588页

作者： Hong-Qiang CHENG1 and Gen-Jun XU1,2.Institute of Biochemistry and Cell Biology, shanghai institutes for biological sciences, chinese academy of sciences, {2., {3. 2.ollege of Life Science, Zhejiang University of sciences, Hangzhou 3.003., {3. Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences College of Life Science Zhejiang University of Sciences

Human group IB phospholipase A2.(IB-PLA2. and its zymogen (proIB-PLA2. were purified from E. coli. Refolding was carried out by diluting the denatured forms of both IB-PLA2.and proIB-PLA2. with renaturation buffer in which the disulfide bonds were completely reduced. The refolding yield of proIB-PLA2.was increased by about 50% over that of the mature enzyme. The refolding of IB-PLA2.usually produced aggregates under normal conditions, as determined by light scattering. In addition, the unfolding experiments showed that the mature enzyme was more stable than the proenzyme toward denaturants in the presence of DTT. Results suggested that the N-terminal sequence rather than its conformation of human proIB-PLA2.played an important role in the refolding process.

关键词： human group IB phospholipase A2.(IB-PLA2. refolding first disulfide bond propeptide

Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations

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Acta Pharmacologica Sinica 2004年第12期25卷 146-152页

作者： xiao-hui CAI, Qing ZHANG, Da-fu DING2.Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, shanghai institutes for biological sciences, {2., Graduate School of the {2., shanghai 2.003., china Key Laboratory of Proteomics Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai 200031 China

AIM: To model the three-dimensional structure and investigatethe interaction mechanism ofthe proprotein convertase furin/kexin and their inhibitors (eglin c mutants). METHODS: The three-dimensional complex structures of furin/ kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newly published X-ray crystallographical structures of mouse furin and yeast kexin as templates. The electrostatic interaction energy of each complex was calculated and the results were compared with the experimentally determined inhibition con- stants to find the correlation between them. RESULTS: High quality models of furin/kexin-eglin c mutants were obtained and used for calculation of the electrostatic interaction energies between the proteases and their inhibitors. The calculated electrostaticenergies of interaction showeda linear correlation to the experimental inhibition constants. CONCLUSION: The modeled structures give good explanations of the specificity of eglin c mutants to furin/ kexin. The electrostatic interactions play important roles in inhibitory activity of eglin c mutants to furin/kexin. The results presented here provided quantitative structural and functional information concerning the role of the charge- charge interactions in the binding of furin/kexin and their inhibitors.

关键词： furin kexin eglin c drug design electrostatic mutation

Recent progress in neurodegenerative disorder research in china

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Science china(Life sciences) 2010年第3期53卷 348-355页

作者： ZHOU JiaWei Institute of Neuroscience,shanghai institutes for biological sciences,chinese academy of sciences,{2.,{3. 1. Institute of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

Neurodegenerative disorders,including Alzheimer's disease(AD) and Parkinson's disease(PD),are common disorders of the central nervous system among aging *** the last 10 years insights concerning the etiology,diagnosis and pathogenesis of these diseases have come from research carried out by chinese *** findings include the description of chinese patients with autosomal recessive early-onset PD,the function of the tau protein,molecular mechanisms underlying protein aggregation,and the identification of biomarkers for AD diagnosis and molecules/compounds with potential neuroprotective activities.

关键词： neurodegenerative disorders pathogenesis diagnosis neuroprotection Alzheimer’s disease Parkinson’s disease