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检索条件"任意字段=中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议"

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TOPK inhibits autophagy by phosphorylating ULK1 to promote chemoresistance in glioma cells

TOPK inhibits autophagy by phosphorylating ULK1 to promote c...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Hui Lu Changshu Ke Xiaofang Ni Juanjuan Xiao Ruijuan Xiu Qin Tian Huaxiong Pan Ling Zou Fei Wang Tengfei Ma Ping Yuan Lin Liu Jianmin Zhang Wei Jia Qiuhong Duan Feng Zhu Department of Biochemistry and Molecular Biology School of Basic MedicineHuazhong University of Science and Technology Department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Pathology Union HospitalHuazhong University of Science and Technology

TMZ(temozolomide) treatment,as first-line chemotherapy in GBM(glioblastma),faced with drug *** studies emphasize that TMZ resistance is associated with autophagy,but the mechanism remained particularly ***1,as a serine-threonine protein kinase,is the upper-most protein of ULK1 complex and is emerging as a crucial node in autophagy ***,the regulation of ULK1 is not fully ***(T-LAK cell-originated protein kinase) is a member of MAPKK protein family,which is highly expressed in many malignant tumors and can be used as a molecular marker for the diagnosis and prognosis of *** this study,we identified TOPK,an oncokinase,as a novel upstream kinase to phosphorylate ULK1,and TOPK could inhibit autophagy in glioma *** found that TOPK could directly bind with and phosphorylate ULK1 at Ser495,Ser469,and Ser533 in vitro and ex *** phosphorylation of ULK1 at Ser495,Ser469,and Ser533 by TOPK decreased the activity and stability of ***,as the decrease of ULK1 activity will reduce the occurrence of autophagy,we would like to check the induction of *** demonstrated that TOPK could inhibit the induction and progression of autophagy in glioma ***,TOPK inhibition increased the sensitivity of glioma cells to *** discovery sheds light on the problem of TMZ-resistance in GBM treatment.

关键词： TOPK ULK1 autophagy temozolomide chemoresistance

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Linking sno-lncRNA and SPA lncRNAs to Prader-Willi syndrome

Linking sno-lncRNA and SPA lncRNAs to Prader-Willi syndrome

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Huang Wu Qing-Fei Yin Zheng Luo Li Yang Ling-Ling Chen State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of Sciences Key Laboratory of Computational Biology Shanghai CAS-MPG Partner Institute for Computational BiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of Sciences School of Life Science ShanghaiTech University

Prader-Willi syndrome(PWS) is a neuro-developmental genetic disorder characterized with obesity and *** cases of PWS can be attributed to a large(5-6 Mb) paternal deletion of chr15 q11-q13,but the minimal deletion is mapped to the 3'-untranslated region(UTR) of SNURF-SNRPN that expresses dozens of snoRNAs and several lncRNAs including sno-lncRNAs and *** PWS region sno-lncRNAs and SPAs are processed by distinct ***-lncRNAs are derived from introns and processed on both ends by snoRNP machinery,leading to the accumulation of lncRNAs flanked by snoRNA sequences lacking 5'-m7 G caps and 3'-poly(A) *** processing is associated with nascent mRNA 3' processing and kinetic competition between XRN2 trimming and Pol II *** cleavage/polyadenylation of its upstream gene,the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled *** prevents further degradation,and allows continuous Pol II *** lncRNAs form a nuclear accumulation that is enriched in RBPs including TDP43,RBFOX2,and *** of a human PWS embryonic stem cells cellular model by depleting these lncRNAs resulted in altered patterns of RBPs binding and alternative *** of normal and PWS-hESCs to hypothalamic-like neurons showed remarkable gene expression changes,including those have reported functions in controlling of appetites and *** findings suggest that the absence of these sno-processed lncRNAs in PWS patients is linked to PWS pathogenesis.

关键词： PWS sno-lncRNA SPA Alternative splicing Hypothalamic-like neurons

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Accurate and high-throughput, targeted quantification of CpG methylation without DNA extraction and bisulfite treatment

Accurate and high-throughput, targeted quantification of CpG...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Ya Ling Zhao Jun Zhou Zhi Zheng Dept.of Biochemistry and Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Science and School of Basic MedicinePeking Union Medical College

DNA methylations at specific CpG loci have been increasingly utilized as biomarkers for cancer *** multistep procedures of methylation assay such as DNA extraction,bisulfite conversion can decreased sensitivity and accuracy of *** we described a highly reproducible,endonuclease-based,quantitative and high throughput CpG methylation assay that does not involve DNA extraction and bisulfite conversion,with an ELISA-like workflow on one 96-well *** DNA lysed from blood sample is captured directly to 96-well plate by sandwich hybridization,the ligation products are treated with methylation-sensitive restriction endonuclease,which will cleave at specific unmethylated-cytosine residues while leaving the methylated ones *** buffer change,PCR amplification is performed with a universal *** methylation percentage levels are quantified via delta Cq with real-time *** showed the capture efficiency of our assay was close to 100%.We also observed the significantly better sensitivity of our extraction-free assay than using extracted DNA from the same amount of *** DNA samples with methylation levels range from 0%–100%,a linear regression analysis revealed quantitative and reproducible recovery across the entire methylation *** a significantly simplified procedure and a much higher throughput,our assay efficiently offered overall better accuracy of the measured methylation percentage values than obtained from methylight and gold standard pyrosequencing of the same *** feasibility of multiplex quantitative CpG methylation assessment using MOLDITOF mass spectrometry will alsobe *** no need for nucleic acid purification and bisulfate conversion,our method provides an accurate quantitative CpG methylation assay suitable for high-throughput applications.

关键词： CpG methylation Quantification Accurate High-throughput

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Multifaceted functions of a human aminoacyl-tRNA synthetase in protein synthesis and beyond

Multifaceted functions of a human aminoacyl-tRNA synthetase ...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Ru-Juan Liu Tao Long Hao Li En-Duo Wang State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences School of Life Science and Technology ShanghaiTech University

Aminoacyl-tRNA synthetases(aaRSs) are prominently known for their conventional function of generating aminoacylt RNAs to provide material for protein ***,beyond protein synthesis,aaRSs have been shown to exhibit other essential nonconventional functions independent of their catalytic *** human cytosolic leucyl-tRNA synthetase(LeuRS) is one of the most multifaceted aaRS: beside the activity of catalyzing the covalently ligation of leucine to tRNALeus,it could also hydrolyze the mischarged tRNAs,meanwhile,it forms a big MSC complex with other seven aaRSs and scaffold proteins in vivo;most intriguingly,LeuRS could regulated the activity of mTOR pathway which is essential for cell nutrient sensing and active in cancer development;even more,the overexpression of LeuRS was found to be closely related with colon cancer makes LeuRS a convincing target for anti-tumor drug *** structure of LeuRS from eukaryote is remaining unclear for years due the complexity of multi-domains and dynamic property of *** we solve the fulllength structure of human cytosolic LeuRS(hcLeuRS),which contains 1176 amino acid residues with four domains and several connection ***,the architecture of hcLeuRS is similar to LeuRS from archrea but different to that from bacteria distinguished by the insertion site of editing CP1 *** interactions between hcLeuRS and tRNA or the mTOR pathway proteins were studied by biophysical *** on the structure,we further investigate the binding affinity of different series of compounds targeting to either the aminoacylation domain,or the editing domain or the protein interaction *** also solved the complex structure of hcLeuRS with some of the ***,our study provide structural basis for both understanding the multifaceted functions of hcLeuRS and also for drug development targeting to hcLeuRS.

关键词： Aminoacyl-tRNA synthetases multifaceted functions structure drug development

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Purification and crystallization of Aspergillus fumigatus chitinase Af ChiA1 and Af ChiB1

Purification and crystallization of Aspergillus fumigatus ch...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Nan Wu Jun Yang Qing Yang Dalian University of Technology Life Science and Technology College

Aspergillus fumigatus is a filamentous airborne saprophytic fungus and regarded as one of the most pernicious pathogens in immunosuppressed individuals,particularly among patients undergoing cytotoxin chemotherapy or bone-marrow *** spectrum and burden of clinical disease due to *** is becoming increasingly recognised.A limited therapeutic arsenal against increasing clinical disease due to Aspergillus *** urgent characterisation of new antifungal *** in filamentous fungi have been shown to be involved in a variety of functions such as cell wall digestion,germination of spores,hyphal growth,hyphal autolysis,differentiation into spores,assimilation of chitin and *** we selected *** glycosyl hydrolases 18 family plant-type chitinase A1(Af ChiA1) and bacterial-type chitinase B1(Af ChiB1) as potential antifungal therapeutic *** use the yeast Pichia pastoris expression system and the Escherichia coli strain BL21(DE3) expression system to acquire Af ChiA1 and Af ChiB1 which containing purification tag,and the expression was confirmed by SDS-PAGE and *** purified target protein was obtained by using metal affinity chromatography and exclusion *** the optimum temperature and optimum pH of the target protein were then *** get the crystals of the two target protein through hanging vapor diffusion methods by using the crystal screening *** crystal structures were obtained by X-RAY *** order to preferably inhibit growth and invasion of filamentous fungi ***,subsequent experiments will screen inhibitors against Af ChiA1 and Af *** is desirable that the compounds with excellent inhibitory effect can be obtained as a skeleton of a novel antifungal drug.

关键词： Aspergillus fumigatus Antifungal target Chitinase AfChiA1 AfChiB1 Crystallization Inhibitors

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Identification, Characterization and Functional Investigation of Circular RNAs in SVZ of Adult Rat Brain

Identification, Characterization and Functional Investigatio...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Fang Xie Yun Zhao Shi-Da Wang Jing Ma Liang Zhang Xue Wang Ling-Jia Qian Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences

Adult neural stem cells(NSCs) are able to self-renew and generate new neural *** regulators of NSCs is significant for the development of NSC-based therapies for neurodegenerative diseases and brain ***,circular RNAs(circRNAs) have been characterized in various cell lines and brain tissues,and found to participate in multiple biological ***,the expression pattern of circRNAs in adult NSCs is still ***,the subventricular zone(SVZ) of the lateral ventricle was isolated as the niche of NSCs in adult rat brain for RNA *** the characteristics of circRNAs profiling in both SVZ and cerebral cortex were also *** a result,29049 and 31975 circRNAs were identified in SVZ and cortex,*** them,41 were SVZ-specific and 48 were cortex-specific.467 circRNAs were also found to express predominately in SVZ,while the cortex had other 423 regnant *** ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed that the SVZ-specific circRNAs have closely relationship with the regulation of NSC expansion and NSC-niche interaction,while the other differentially expressed circRNAs might be involved in neural cellular construction and nerves system ***,the interactions between circRNAs and microRNAs were also explored,and the result showed that one SVZ-specific circRNA was capable to competitively bind miR-138-5 p as a potential derepressive regulator in NSCs ***,our work has laid the foundations to decipher regulation mechanisms of circRNAs in adult NSCs and to develop circRNAs as novel biomarkers for adult NSCs.

关键词： circular RNA neural stem cell subventricular zone RNA-seq microRNA

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GIPC2, a novel tumor suppressor gene in pheochromocytoma, activates the expression of p27 through NONO

GIPC2, a novel tumor suppressor gene in pheochromocytoma, ac...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Yeqing Dong Zhengguang Guo Liang Wang Chengyan Fan Zhi Zheng Dept.of Biochemistry and Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Science and School of Basic MedicinePeking Union Medical College

GIPC2 is a member of the GIPC family which regulates various cellular processes,including proliferation,cytoplasmic division and *** expression level of GIPC2 changes in a variety of *** example,GIPC2 is upregulated in gastric cancer,while downregulated in kidney ***,GIPC2 function in the tumorigenesis is still *** this study,we found that GIPC2 was low expressed in pheochromocytoma ***2 was mainly located in the nucleus,which affected cell cycle,inhibited cell proliferation and tumor growth,and activated the expression of tumor suppressor p27 *** further discover the molecular mechanism of GIPC2,immunoprecipitation-mass spectrometry method was used to identify GIPC2 interaction proteins.A Nuclear located protein,NONO was identified as a candidate GIPC2 interaction ***,the interaction between GIPC2 and NONO was verified using GST pull-down,fluorescence resonance energy transfer and ***,we found that NONO can also activate the expression of p27 *** NONO blocked GIPC2 mediated p27 ***,we found NONO might serve as a transcription factor which increased p27 promoter activity mainly via binding to the-34/+1 region of p27 ***,our study indicates that GIPC2 acts as a novel tumor suppressor gene in pheochromocytoma and activates the expression of p27 through *** results provide the molecular mechanism for future studying the biological functions of GIPC2 in the tumorigenesis.

关键词： GIPC2 pheochromocytoma Interaction protein Tumor suppressor

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Decreased expression of subunit 3 of molecular chaperone TRiC suppresses proliferation of esophageal carcinoma

Decreased expression of subunit 3 of molecular chaperone TRi...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Lifang Wang Wenhu Chen Peng Du Taobo Luo Zhiguo Zhen Jiajia Chen Zexin Fu Hongguang Zhao Department of Biochemistry Institute of Basic Medical ScienceHangzhou Medical College Department of Thoracic Surgery Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology(Lung and Esophagus)Zhejiang Cancer Hospital Department of Clinical Medicine Hangzhou Medicine College Wenzhou Medical University

OBJECTIVE: To investigate the value of subunit 3 of molecular chaperone TRiC(CCT3) to determine its function in esophageal carcinoma(EC) ***: CCT3 expression levels were examined in EC cell lines by quantitative real time *** expression was suppressed by small interfering RNA and the effects of reducing CCT3 expression in TE-1 cells were *** proliferation rate,cell cycle and apoptosis were detected to evaluate cell functions in *** change of key signal molecules in cell signal pathways was detected in TE-1 cells after RNA interference with Ingenuity Pathway Analysis and PathScan RTK Signaling Antibody ***: The expression levels of CCT3 mRNA and protein were up-regulated in EC cell *** CCT3 expression suppressed cell proliferation and induced cell apoptosis with high caspase 3/7 activity(P<0.05 vs negative control).Cells with G1 phase decreased(P <0.05),while the number of cells in the S phase increased(P <0.05).In stress and apoptosis signaling pathway,phosphorylation level of P38 MAPK were significantly up-regulated(P <0.05) after CCT3 gene was ***: Highly expressed subunit 3 of molecular chaperone TRiC effects esophageal squamous cell development by inhibiting phosphorylation of P38 MAPK.

关键词： esophageal canrcinoma Chaperonin Containing TCP1 Subunit 3 Cell proliferation

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PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma

PRMT2 links histone H3R8 asymmetric dimethylation to oncogen...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Feng Dong Qian Li Chao Yang Chunsheng Kang Xudong Wu Department of Cell Biology Tianjin Medical University2011 Collaborative Innovation Center of Tianjin for Medical EpigeneticsTianjin Key Laboratory of Medical Epigenetics Department of Neurosurgery Tianjin Medical University General Hospital and 3Laboratory of Neuro-OncologyTianjin Neurological Institute

Transcriptional deregulation plays a vital role in Glioblastoma multiforme(GBM).Thus,identification of epigenetic modifiers essential for oncogenic transcriptional programs is a key to designing effective therapeutic strategies for this deadly *** roles of protein arginine methyltransferases(PRMTs) as epigenetic regulators in cancers are poorly *** we show that PRMT2 is highly expressed in GBM and correlated with poor *** silencing of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro and suppreses orthotopic tumor *** analysis demonstrated that PRMT2 depletion leads to significant deregulation of genes mainly associated with cell cycle progression and pathways in *** agreement with published results,we show that PRMT2 is responsible for H3 R8 asymmetric methylation(H3 R8 me2 a) and that H3 R8 me2 a enrichment at promoters and enhancers is closely correlated with known active histone ***,we show that PRMT2-mediated H3 R8 me2 a is required for the maintenance of target gene expression and that the catalytic activity of PRMT2 is required for its protumorigenic *** together,this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.

关键词： glioblastoma epigenetic arginine methylation

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Runx2 mediated misregulation of Osteopontin splicing promoted Epithelial-Mesenchymal Transition in non-small cell lung cancers

Runx2 mediated misregulation of Osteopontin splicing promote...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Jing Huang Siyuan Chang Shan Cheng Department of Biochemistry and Molecular Biology School of Basic MedicineCapital Medical University Beijing Key Laboratory for Cancer Invasion and Metastasis Research

Background: Osteopontin(OPN) is a phosphorylated glycoprotein frequently overexpressed in cancers,including lung cancer in *** OPN splicing isoforms(OPN-SI) of OPNa,OPNb and OPNc were demonstrated to have specific activities in different tumor *** work aims to investigate the levels and the regulation of OPN-SI during epithelial-mesenchymal transition(EMT) in non-small-cell lung cancer(NSCLC).Methods: The mRNA levels of OPNSI,Runx2 and EMT markers of E-cadherin,N-cadherin,snail family transcriptional repressor 1(SNAI1) and snail family transcriptional repressor 2(SLUG) were determined by qRT-PCR and/or western blot in A549 cells before and after EMT ***: The expression levels of OPNa,OPNb and OPNc significantly increased in the TGF-β1-induced A549 cells,which exerted fibroblast-like morphology as EMT *** expression of EMT-related genes changed accordingly with the morphologic observations and cell behavior in ***,as a major form of OPN,significantly increased at mRNA levels during EMT,correlating to the increased expression of ***,in EMT cells the levels of OPNc mRNA dramatically increased as shown by the ratio of OPNc to *** the cells treated with TSA,the HDACs inhibitor,the Runx2-stimulated the increase of the ratio changes in OPNc to OPNa ***: These data suggested that OPN-c appeared to be a more important protein marker to indicate the occurance of EMT in non-small cell lung *** factor Runx2 not only enhanced the mRNA transcription of opn gene,but also regulated of OPN mRNA *** regulators,such as HDAC,need to be considered,primarily for its interaction with specific transcription factors.

关键词： Osteopontin RNA splicing EMT NSCLC

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