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A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir

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Cell Research 2007年第4期17卷 357-362页

作者： Chuan-Yun Li~(1,*) Quan Yu~(2,*) Zhi-Qiang Ye~(1,*) Ying Sun~1 Quanyuan He~(1,3) Xiao-Mo Li~1 Wuxue Zhang~1 Jingchu Luo~1 Xiaocheng Gu~1 Xiaofeng Zheng~2 Liping Wei~1 ~1Center for Bioinformatics,~2Department of Biochemistry and Molecular Biology,National Laboratory of Protein Engineering and Plant Genetic Engineering,college of life sciences,peking university,beijing 100871,china ~3Laboratory of Biochemistry,college of life sciences,Hunan Normal university,Changsha 410081,china Center for Bioinformatics National Laboratory of Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing China Department of Biochemistry and Molecular Biology National Laboratory of Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing China Laboratory of Biochemistry College of Life Sciences Hunan Normal University Changsha China

The use of oseltamivir,widely stockpiled as one of the drugs for use in a possible avian influenza pandemic,has beenreported to be associated with neuropsychiatric disorders and severe skin reactions,primarily in *** we identi-fied a nonsynonymous SNP(single nucleotide polymorphism)in dbSNP database,R41 Q,near the enzymatic active siteof human cytosolic sialidase,a homologue of virus neuraminidase that is the target of *** SNP occurredin 9.29% of Asian population and none of European and African American *** structural analyses and Kimeasurements using in vitro sialidase assays indicated that this SNP could increase the unintended binding affinity ofhuman sialidase to oseltamivir carboxylate,the active form of oseltamivir,thus reducing sialidase *** addition,this SNP itself results in an enzyme with an intrinsically lower sialidase activity,as shown by its increased Km anddecreased Vmax *** administration of oseltamivir to people with this SNP might further reduce theirsialidase *** note the similarity between the reported neuropsychiatric side effects of oseltamivir and the knownsymptoms of human sialidase-related *** propose that this Asian-enriched sialidase variation caused by theSNP,likely in homozygous form,may be associated with certain severe adverse reactions to oseltamivir.

关键词： Asia SNP neuraminidase inhibitor oseltamivir sialidase bioinformatics

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Sequential Phosphorylation of Nedd1 by Cdk1 and Plk1 is required for γTuRC targeting to centrosome

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生物物理学报 2009年第S1期25卷 245-246页

作者： Xiaoyan Zhang, Qiang Chen, Qing Jiang and Chuanmao Zhang The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, college of life sciences, peking university, beijing 100871, china

Nedd1 (neural precursor cell expressed, developmentally down-regulated gene 1) is an evolutionarily conserved protein that has previously been characterized as a new member

关键词： Sequential Phosphorylation of Nedd1 by Cdk1 and Plk1 is required for TuRC targeting to centrosome

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Short exposure to paclitaxel induces multipolar spindle formation and aneuploidy through promotion of acentrosomal pole assembly

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Science china(life sciences) 2010年第11期53卷 1322-1329页

作者： BIAN MingLei1, FU JingYan1, YAN Yan1, CHEN Qiang1, YANG Chao2, SHI QingHua2,JIANG Qing1 & ZHANG ChuanMao1 1MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, college of life sciences, peking university, beijing 100871, china 2Hefei National Laboratory for Physical sciences at Microscale and School of life sciences, university of Science and Technology of china, Hefei 230026, china MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering College of Life Sciences Peking University Beijing China Hefei National Laboratory for Physical sciences at Microscale and School of life sciences University of Science and Technology of China Hefei China

Paclitaxel is a widely used microtubule drug and cancer medicine. Here we report that by short exposure to paclitaxel at a low dose, multipolar spindles were induced in mitotic cells without centrosome amplification. Both TPX2 depletion and Aurora-A overexpression antagonized the multipolarity. Live cell imaging showed that some paclitaxel-treated cells accomplished multipolar cell division and a portion of the daughter cells went on to the next round of mitosis. The surviving cells grew into clones with varied genome content. The results indicated that an aneuploidy population could be induced by short exposure to paclitaxel at a low dose, implicating potential side effects of paclitaxel.

关键词： paclitaxel tpx2 Aurora-A multipolar cell division aneuploidy

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RIPL, a Potent Inducer of Apoptosis

RIPL, a Potent Inducer of Apoptosis

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中国细胞生物学学会第八届会员代表大会暨学术大会

作者： Jikun Zha Hongbing Shu Department of Cell Biology and Genetics, college of life sciences, peking university, beijing 100871, china,

Receptor-interacting protein(RIP) is a Serine/threonine protein kinase that iscritically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-κBactivation. Here we report the cloning and characterization of a novel RIP-homologous molecule *** contains a kinase domain. Overexpression of RIPLinduced cell death with characteristic apoptotic *** can induce DNA

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Arabidopsis AtBECLIN 1/AtAtg6/AtVps30 is essential for pollen germination and plant development

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Cell Research 2007年第3期17卷 249-263页

作者： Genji Qin~1 Zhiqiang Ma~1 Li Zhang~1 Shufan Xing~1 Xianhui Hou~1 Jie Deng~1 Jingjing Liu~1 Zhangliang Chen~(1,2) Li-Jia Qu~(1,2) Hongya Gu~(1,2) ~1National Laboratory for Protein Engineering and Plant Genetic Engineering,peking- Yale Joint Research Center for Plant Molecular Genetics and AgroBiotechnology,college of life sciences,peking university,beijing 100871,china ~2The National Plant Gene Research Center (beijing),beijing 100101,china National Laboratory for Protein Engineering and Plant Genetic Engineering Peking-Yale Joint Research Center for Plant Molecular Genetics and AgroBiotechnology College of Life Sciences Peking University Beijing 100871 China The National Plant Gene Research Center (beijing) Beijing 100101 China

Pollen germination on the surtace ot compatible stigmatic tissues is an essential step tor plant *** wereport that the Arabidopsis mutant bcl1 is male sterile as a result of the failure of pollen *** show that the bcl1mutant allele cannot be transmitted by male gametophytes and no homozygous bcl1 mutants were *** ofpollen developmental stages indicates that the bcl1 mutation affects pollen germination but not pollen ***-lar analysis demonstrates that the failure of pollen germination was caused by the disruption of AtBECLIN ***1 is expressed predominantly in mature pollen and encodes a protein with significant homology to Beclin1/Atg6/Vps30required for the processes of autophagy and vacuolar protein sorting(VPS)in *** also show that AtBECLIN 1 isrequired for normal plant development,and that genes related to autophagy,VPS and the glycosylphosphatidylinositolanchor system,were affected by the deficiency of AtBECLIN 1.

关键词： Arabidopsis thaliana AtBECLIN 1 pollen germination plant normal development

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NIK is a component of the EGF/heregulin receptor signaling complexes

NIK is a component of the EGF/heregulin receptor signaling c...

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中国细胞生物学学会第八届会员代表大会暨学术大会

作者： Danying Chen Hong-Bing Shu Department of Cell Biology and Genetics, college of life sciences, peking university, beijing 100871, china

Nuclear factor кB-inducing kinase (NIK) is a member of the MAP kinase kinasekinase family that was identified as a component of the TNF-R1 -induced NF-кBactivation pathway (TNF, tumor necrosis factor;NF-кB, nuclear factor kappaB,). Geneknockout study, however, suggests that NIK is dispensable for TNF-R1- but required forlymphotoxin-βreceptor-induced NF-кB activation. A NIK kinase inactive mutant is a

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SINK:a p65-interacting negative regulator of NF-kB-dependent transcription

SINK:a p65-interacting negative regulator of NF-kB-dependent...

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中国细胞生物学学会第八届会员代表大会暨学术大会

作者： Min Wu Hong-Bing Shu Department of Cell Biology and Genetics, college of life sciences, peking university, beijing 100871, china,

The transcription factor NF-кB plays important roles in inflammation and cellsurvival. In this study, we identified SINK, an NF-кB -inducible protein. Overxpressionof SINK inhibited NF-кB -dependent transcription induced by TNF stimulation or itsdownstream signaling proteins, but did not inhibit NF-кB translocation to the nucleus andbinding to DNA. Co-immunoprecipitation and in vitro kinase assays indicated that SINK

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Cloning and characterization of DcLEA1,a new member of carrot LEA gene family

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Progress in Natural Science:Materials International 2005年第3期 28-36页

作者： LIU Yiming 1,2 ,DIAO Fengqiu 1 ,ZHANG Lei 1 ,HUANG Meijuan 2 and WU Naihu 1ˇˇ (1.Institute of Genetics and Developmental Biology,Chinese Academy of sciences,beijing100080,china 2.college of life sciences,peking university,beijing100871,china) Institute of Genetics and Developmental Biology，Chinese Academy of sciences，beijing 100080，china college of life sciences Peking University，Beijing 100871，China Institute of Genetics and Developmental Biology，Chinese Academy of sciences，beijing 100080，china college of life sciences Peking University，Beijing 100871，China

Using a modified cDNA representational difference analysis(RDA)method,a LEA gene fragment was isolated from the regulated carrot somatic embryo,which was used as the probe to screen the cDNA library of the regulated carrot somatic embryo and the genomic library constructed by the method of altering osmotic *** analysis showed that it is homologous to LEA gene family and designated as DcLEA1(GenBank number:AF308739),a new member of the carrot LEA gene *** transcription re-gion contains5′UTR,two exons,one intron and3′UTR region;its coding region is480bp long,coding for159amino acids and one stop *** hybridization indicated that DcLEA1gene was not expressed in the adult carrot but expressed at high levels in the regulated carrot somatic *** carrot somatic embryo which had been deregulated for12hours,the expression levels dropped rapid-ly;with the prolongation of deregulation,the radicle of carrot somatic embryo began to stretch,and the expression level of DcLEA1gene *** phenomenon is similar to the expression pattern of LEA gene in the course of dormancy and germination of the seed;thus suggesting that the sucrose regulation-deregulation system of the carrot somatic embryo can be used to mimic plant seed dormancy and ger-mination and can also be used to study the molecular mechanisms of these two biological processes.

关键词： carrot(Daucus carota L.) DcLEA1 development of radicle.

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Identification of a novel regulator in NF-KB signaling pathways

Identification of a novel regulator in NF-KB signaling pathw...

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中国细胞生物学学会第八届会员代表大会暨学术大会

作者： Xiaoqin Su Hong-Bing Shu Department of Cell Biology and Genetics, college of life sciences, peking university, beijing 100871, china

NF-κB is an inducible transcription factor that plays critical roles in manyphysiological responses such as inflammation, apoptosis and immune systemdevelopment. Receptor Interacting Protein (RIP) is an important molecule requiredfor TNF induced NF-κB activation. ZIN, a newly identified zinc finger protein, isdemonstrated to interact with RIP and inhibit RIP induced NF-κB acivation.

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ZNF216 is an A20-like and IKKγ-interacting inhibitor of NFkappa B activation

ZNF216 is an A20-like and IKKγ-interacting inhibitor of NFk...

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中国细胞生物学学会第八届会员代表大会暨学术大会

作者： Jun Huang Hong-Bing Shu Department of Cell Biology and Genetics, college of life sciences, peking university, beijing 100871, china,

The transcription factor NF-κB play importare roles in immun regulation,inflammatory responses and ati-apoptosis. Activation of NF-κB requires theactivity of IKK, a kinase complex that contains two catalytic subunit...

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