检索结果-南通市图书馆

Deacetylation of MTHFD2 by SIRT4 senses stress signal to inhibit cancer cell growth by remodeling folate metabolism

在线全文

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2022年第4期14卷 39-50页

作者： Fan Zhangi: Di Wangl- intao Li Ying Su Suling Liu Qun-Ying Lei Miao Yin Fudan University Shanghai cancer Center Instutes of Biomedical Science&School fasic Medical Sciences CancerlnstesKey Laboratory of Breast Cancer in ShanghaiShanghai Key Laboratory of Radiation OncologyThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Oncology Shanghai Medical CllegeFudan UniversityShanghai 200032China State Key laboratory of Medical Neurobiology Fudan UniversityShanghai 20o032China

Folate metabolism plays an essential role in tumor *** cancers display therapeutic response to reagents targeting key enzymes of the folate cycle,but obtain chemoresistance ***,novel targets in folate metabolism are highly *** dehydrogenase/methylenetetrahydrofolate cyclohydrolase 2(MTHFD2)is one of the key enzymes in folate metabolism and its expression is highly increased in mutiple human ***,the underlying mechanism that regulates MTHFD2 expression remains ***,we elucidate that SIRT4 deacetylates the conserved lysine 50(K50)residue in MTHFD2.K50 deacetylation destabilizes MTHFD2 by elevating cullin 3 E3 ligase-mediated proteasomal degradation in response to stressful stimuli of folate deprivation,leading to suppression of nicotinamide adenine dinucleotide phosphate production in tumor cells and accumulation of intracellular reactive oxygen species,which in turn inhibits the growth of breast cancer ***,our study reveals that SIRT4 senses folate availability to control MTHFD2 K50 acetylation and its protein stability,bridging nutrient/folate stress and cellular redox to act on cancer cell growth.

关键词： folate metabolism MTHFD2 CUL3 SIRT4 acetylation breast cancer

Functions of PARylation in DNA Damage Repair Pathways

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genomics, Proteomics & Bioinformatics 2016年第3期14卷 131-139页

作者： Huiting Wei Xiaochun Yu Department of Immunology Tianjin Key Laboratory of Cellular and Molecular ImmunologyMOE Key Laboratory of Immune Microenvironment and DiseaseSchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of cancer Genetics and epigenetics.Beckman Research Institute City of Hope Medical CenterDuarteCA 91010USA

Protein poly ADP-ribosylation（PARylation） is a widespread post-translational modification at DNA lesions,which is catalyzed by poly（ADP-ribose） polymerases（PARPs）.This modification regulates a number of biological processes including chromatin reorganization,DNA damage response（DDR）,transcriptional regulation,apoptosis,and ***1,functioning as a DNA damage sensor,can be activated by DNA lesions,forming PAR chains that serve as a docking platform for DNA repair factors with high biochemical ***,we highlight molecular insights into PARylation recognition,the expanding role of PARylation in DDR pathways,and the functional interaction between PARylation and ubiquitination,which will offer us a better understanding of the biological roles of this unique post-translational modification.

关键词： Poly ADP-ribosylation PARPs DNA damage response PAR-binding modules Ubiquitination

Formation and repair of DNA-protein crosslink damage

在线全文

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2017年第10期60卷 1065-1076页

作者： Naeh L.Klages-Mundt Lei Li Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA Program in Genetics and epigenetics The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston TX 77030 USA

DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks(DPCs)—the covalent linkage of proteins with a DNA strand—are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated *** excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.

关键词： DNA-protein crosslinks nucleotide excision repair SPRTN Fanconi anemia

Structural Basis of RACK7 PHD Domain to Read a Pediatric Glioblastoma-Associated Histone Mutation H3.3G34R

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Chemistry 2021年第9期39卷 2433-2440页

作者： Wenxian Lan Ze Li Fangfang Jiao Chunxi Wang Rui Guo Chunyang Cao State Key laboratory of Bioorganic and Natural Product Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryChinese Academy of Sciences345 Ungling RoadShanghai 200032China Fudan University Shanghai cancer Center Institute of Biomedical SciencesState Key Laboratory of Genetic Engineering and Shanghai Key Laboratory of Medical EpigeneticsShanghai Medical College of Fudan UniversityShanghai 200032China Center for Medical Research and Innovation Shanghai Pudong HospitalFudan UniversityPudong Medical Centerand the Shanghai Key Laboratory of Medical Epigeneticsthe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyInstitutes of Biomedical SciencesFudan UniversityShanghai 200032China University of Chinese Academy of Science No.19AYuquan RoadShijingshan DistrictBeijing 100049China

Histone point mutations,including missense mutations on histone H3 at positions 27(K27M),34(G34R/V,G34W,G34L)and 36(K36M),were identified as potential cancer driver mutations.H3.3G34R/V mutations account for pediatric glioblastomas(GBM).RACK7(also known as ZMYND8,PRKCBP1)was recently reported to specifically bind H3.3G34R through its PHD(plant homedomain)domain(PHDRACK7)in vitro and in H3.3G34R pediatric glioblastoma cells,playing key roles in H3.3G34R-mediated gene ***,we provided both biochemical and NMR structural evidences that PHDRACK7 recognized histone H3.3G34R mutant via a mechanism distinet from all other reported PHD *** the reported residue D104,two new sites D108 and L121 of PHD^(RACK7) were found necessary for the interactions between PHD^(RACK7) and histone H3.3G34R *** results provided a potential molecular basis for pediatric GBM driven by the H3.3G34R mutation.

关键词： RACK7 H3.3G34R Interaction NMR Structure

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of cancer 2013年第1期32卷 3-11页

作者： Ji-Sheng Li Jian-Ming Ying Xiu-Wen Wang Zhao-Hui Wang Qian Tao Li-Li Li Department of Chemotherapy Cancer CenterQilu HospitalShandong University Department of Pathology Cancer Hospital & InstitutePeking Union Medical College and Chinese Academy of Medical Sciences cancer epigenetics laboratory Department of Clinical OncologySir YK Pao Center for Cancer and Li Ka Shing Institute of Health SciencesThe Chinese University of Hong Kong Hong Kong and CUHK Shenzhen Research Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences(CAS)-CUHK

Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian *** silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and ***,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis *** review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.

关键词：基因启动子抑癌基因鳞状细胞癌食管癌甲基化肿瘤抑制基因肿瘤标志物表观遗传

STING cg16983159 methylation:a key factor for glioblastoma immunosuppression

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2022年第8期7卷 2638-2640页

作者： Lei Qiu Yang Meng Junhong Han Research laboratory of Tumor epigenetics and Genomics Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer Centerand National Clinical Research Center for GeriatricsWest China HospitalSichuan University610041 ChengduP.R.China

In a recent study published in cancer Cell,Low et *** a light on a novel DNA methylation pattern in the promoter region of the stimulator of interferon genes(STING),which may be a key factor for the“cold”tumor micro-environment(TME)of glioblastoma(GBM),contributing to its immunosuppression.1 They have demonstrated that STING expression is epigenetically silenced by cg16983159 methylation in glioma cells as well as normal brain cells and this silencing can be rescued by DNA methyltransferase(DNMT)inhibition(Fig.1).

关键词： al. interferon glioblastoma

Ubiquitin ligase DTX3 empowers mutant p53 to promote ovarian cancer development

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genes & Diseases 2022年第3期9卷 705-716页

作者： Shanshan Wang Qian Hao Jiajia Li Yajie Chen Hua Lu Xiaohua Wu Xiang Zhou Fudan University Shanghai cancer Center and Institutes of Biomedical Sciences Fudan UniversityShanghai 200032PR China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032PR China Department of Gynecological Oncology Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Department of Radiation Oncology Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Department of Biochemistry&Molecular Biology and Tulane cancer Center Tulane University School of MedicineNew OrleansLA 70112USA Key laboratory of Breast cancer in Shanghai Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032PR China Shanghai Key laboratory of Medical epigenetics International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyInstitutes of Biomedical SciencesFudan UniversityShanghai 200032PR China

The deltex family protein DTX3 is believed to possess E3 ubiquitin ligase activity,as it contains a classic RING finger ***,its biological role and the underlying mechanism in cancer remain largely ***,we identified DTX3 as a novel mutant p53-interacting protein in ovarian ***,DTX3 mediated mutant p53 ubiqui-tination and stabilization by perturbing the MDM2-mutant p53 interaction,consequently leading to activation of *** p53 target ***,a positive correlation between the expression of DTX3 and mutant p53 target genes was further validated in ovarian *** DTX3 promoted,while depletion of DTX3 suppressed,ovarian cancer cell proliferation and ***,the pro-tumorigenic effect of DTX3 is dependent on mutant p53,because ablation of mutant p53 significantly impaired DTX3-induced gene expression and ovarian cancer cell growth and ***,DTX3 elevated the expressi on of muta nt p53 target genes and boosted ovarian tumor growth in *** ally,DTX3 was amplified and overexpressed in ovarian carci no mas,which is sign ificantly associated with unfavorable ***,our findings unveil the oncogenic role of DTX3 in ovarian cancer development by bolstering mutant p53 activity.

关键词： DTX3 E3 ubiquitin ligase Invasion Mutant p53 Ovarian cancer Proliferation

The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

cancer Drug Resistance 2021年第2期4卷 365-381页

作者： Yang Meng Lei Qiu Su Zhang Junhong Han Research laboratory of cancer epigenetics and Genomics Department of General SurgeryFrontiers Science Center for Disease-related Molecular NetworkCancer Center and National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

Epithelial cancer of the ovary exhibits the highest mortality rate of all gynecological malignancies in women today,since the disease is often diagnosed in advanced *** the treatment of cancer with specific chemical agents or drugs is the favored treatment regimen,chemotherapy resistance greatly impedes successful ovarian cancer ***,chemoresistance becomes one of the most critical clinical issues confronted when treating patients with ovarian *** evidence hints that dysregulation of E3 ubiquitin ligases is a key factor in the development and maintenance of ovarian cancer *** review outlines recent advancement in our understanding of the emerging roles of E3 ubiquitin ligases in ovarian cancer *** also highlight currently available inhibitors targeting E3 ligase activities and discuss their potential for clinical applications in treating chemoresistant ovarian cancer patients.

关键词： Ovarian cancer chemoresistance E3 ubiquitin ligases inhibitor

N-linked glycoproteomic profiling in esophageal squamous cell carcinoma

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2022年第29期28卷 3869-3885页

作者： Qi-Wei Liu Hao-Jie Ruan Wei-Xia Chao Meng-Xiang Li Ye-Lin Jiao Douglas G Ward She-Gan Gao Yi-Jun Qi Henan Key laboratory of Microbiome and Esophageal cancer Prevention and Treatment/Henan Key laboratory of cancer epigenetics/cancer Hospital The First Affiliated HospitalCollege of Clinical MedicineHenan University of Science and TechnologyLuoyang 471003Henan ProvinceChina Department of Pathology The First People’s Hospital of Luo YangLuoyang 471000Henan ProvinceChina Institute of cancer and Genomic Sciences College of Medical and Dental SciencesUniversity of BirminghamBirmingham B152TTUnited Kingdom

BACKGROUND Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic *** To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma(ESCC)via two complementary *** Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins,we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis(2-DE)-based and isobaric tags for relative and absolute quantification(iTRAQ)labeling-based mass spectrometry quantitation in parallel,followed by validation of candidate glycoprotein biomarkers by Western *** 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins,respectively,with 15 in common,demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two *** showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with *** blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D,and the downregulation of total haptoglobin,high-mannose clusterin,and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC *** serum levels of glycosylated fractions of clusterin,prolinearginine-rich end leucine-rich repeat protein,and haptoglobin in patients with ESCC were remarkably higher than those in healthy *** Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC,which will be a valuable resource for future investigations.

关键词： Esophageal squamous cell carcinoma N-linked glycoprotein Post-translational modification Lectin Cathepsin D Haptoglobin 14-3-3ζ