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O-GlcNAc修饰与疾病病理学的联系（英文）

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Journal of zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第5期20卷 437-448页

作者： Hao NIE Wen YI moe laboratory of biosystems homeostasis&protection College of Life SciencesZhejiang University

O-连接的N-乙酰葡萄糖胺(O-GlcNAc)修饰是一种发生于蛋白质丝氨酸或苏氨酸残基上的蛋白翻译后修饰,它能动态地发生在细胞的任何部位,如细胞质、线粒体、细胞核等。O-GlcNAc修饰的供体尿苷二磷酸-N-乙酰葡萄糖胺(UDP-GlcNAc)是己糖胺生... 详细信息

O-连接的N-乙酰葡萄糖胺(O-GlcNAc)修饰是一种发生于蛋白质丝氨酸或苏氨酸残基上的蛋白翻译后修饰,它能动态地发生在细胞的任何部位,如细胞质、线粒体、细胞核等。O-GlcNAc修饰的供体尿苷二磷酸-N-乙酰葡萄糖胺(UDP-GlcNAc)是己糖胺生物合成途径(HBP)的终产物。GlcNAc在蛋白上的添加和移除分别需要O-GlcNAc转移酶(OGT)和O-GlcNAc水解酶(OGA)的介导。被O-GlcNAc修饰的蛋白包括转录因子、代谢酶、细胞信号传导因子等。O-GlcNAc通过调控这些蛋白的功能参与到许多重要的生物进程中,如转录、翻译、代谢、信号传导、自噬等。此外,O-GlcNAc修饰的失调还与许多重要疾病息息相关,包括癌症、糖尿病、神经退行性疾病和心血管疾病。更好地了解O-GlcNAc修饰在这些疾病生理病理学进程中所起的作用将有助于开发新的治疗策略。本文介绍了O-GlcNAc与疾病病理联系的最新研究,并揭示O-GlcNAc可作为潜在的临床治疗靶点。

关键词： O连接的N-乙酰葡萄糖胺(O-GlcNAc) 癌症糖尿病神经退行性疾病心血管疾病

小鼠早期胚胎发育中组蛋白修饰H2AK119ub1与H3K27me3的全基因组解偶联

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Science Bulletin 2021年第24期66卷 2489-2497,M0004页

作者：朱业张俞佳丽戎妍吴韵雯李阳张乐姣潘应昊范衡宇沈立 The MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology Life Sciences InstituteZhejiang UniversityHangzhou 310058China Department of Orthopedics Surgery the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Hangzhou Innovation Center Zhejiang UniversityHangzhou 311215China

多梳家族蛋白(Polycomb group proteins)是发育过程中的关键染色质调控因子.组蛋白H2AK119位点的单泛素化修饰(H2AK119ub1,H2Aub)和组蛋白H3K27位点的三甲基化修饰(H3K27me3)分别是由多梳抑制复合体1(Polycomb Repressive Complex,PRC1)和2(PRC2)催化.由于PRC1和PRC2可以相互招募,H2Aub和H3K27me3这两种组蛋白修饰在基因组上表现出很大程度的重合与偶联.然而,它们是否能够独立存在并发挥功能仍然没有定论.本研究新开发了一种超灵敏微量染色质免疫共沉淀测序技术CATCH-Seq,并利用该技术发现H2Aub和H3K27me3在小鼠早期胚胎发育过程中呈现出全基因组范围的解偶联现象,即经典的多梳家族蛋白靶基因上仅有H2Aub的富集,而非经典基因印记区域仅有H3K27me3的富集.这些结果表明,H2Aub能够在早期胚胎发育阶段缺失H3K27me3的情况下负责沉默未来具有二价启动子的基因,但并不直接参与H3K27me3依赖的非经典印记基因的沉默.该工作揭示了H2Aub和H3K27me3这两种组蛋白修饰在哺乳动物早期胚胎发育中相互区别且独立的分布和功能.

关键词：组蛋白修饰解偶联早期胚胎发育染色质免疫共沉淀甲基化修饰印记基因测序技术泛素化修饰

Intercellular transmission of cGAS-STING signaling in cancer

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cancer biology & Medicine 2023年第2期20卷 93-97页

作者： Qirou Wu Xiaohong Leng Pinglong Xu moe laboratory of biosystems homeostasis and protection and zhejiang provincial key laboratory for cancer molecular cell biology Life Sciences InstituteZhejiang UniversityHangzhou 310058China Institute of Intelligent Medicine Hangzhou Global Scientific and Technological Innovation CenterZhejiang University(HIC-ZJU)Hangzhou 310058China cancer Center Zhejiang UniversityHangzhou 310058China

cellular communication is necessary for organizing multicellular organisms,and is critical in tumorigenesis and progression.Immune and tumor cells use the cGAS-STING mechanism to sense and respond to genomic instabili... 详细信息

关键词： damage Immune cancer

外泌体:连接机械力感应和肝癌发生的纽带（英文）

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Science Bulletin 2023年第24期 3087-3090页

作者：唐梅汪辰靓赵斌 moe key laboratory of biosystems homeostasis & protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital School of Medicine Zhejiang University Center for Life Sciences Shaoxing Institute Zhejiang University

Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer, and the third leading cause of cancer-related mortality worldwide. This disease is intimately related to mechanical stress. Most HCCs deve...

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外泌体:连接机械力感应和肝癌发生的纽带

Science Bulletin 2023年第24期68卷 3087-3090页

作者：唐梅汪辰靓赵斌 moe key laboratory of biosystems homeostasis&protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biologyand Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou 310058China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China Center for Life Sciences Shaoxing InstituteZhejiang UniversityShaoxing 321000China

Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,and the third leading cause of cancer-related mortality worldwide.This disease is intimately related to mechanical stress.Most HCCs develop ... 详细信息

Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,and the third leading cause of cancer-related mortality worldwide.This disease is intimately related to mechanical stress.Most HCCs develop in the context of liver fibrosis or cirrhosis,accompanied by increased stiffness.

关键词：肝癌发生外泌体 liver

The cGAS-STING pathway:a therapeutic target in chromosomally unstable cancers

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Signal Transduction and Targeted Therapy 2023年第2期8卷 338-340页

作者： Haiyan Yan Weiguo Lu Fangwei Wang key laboratory of Novel Targets and Drug Study for Neural Repair of zhejiang Province School of MedicineHangzhou City University310015HangzhouChina Women’s Hospital Zhejiang University School of Medicine310006HangzhouChina cancer Center Zhejiang University310058HangzhouChina The moe key laboratory of biosystems homeostasis&protection and zhejiang provincial key laboratory of cancer molecular cell biology Life Sciences InstituteZhejiang University310058HangzhouChina

In a recent study published in Nature,Hong et al.revealed that the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)innate immune pathway is critically required for the IL-6-dependent survival of chromosomally unstable cancer cells,1 implying that chronic inflammation can be therapeutically targeted to kill cancers displaying chromosomal instability(CIN).

关键词： unstable chromosomal therapeutic

Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites

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Journal of zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第12期24卷 1165-1173页

作者： Yanhua MU Jinhua HAN Mingjie WU Zongfang LI Ke DU Yameng WEI Mengjie WU Jun HUANG National-Local Joint Engineering Research Center of Biodiagnosis&Biotherapy The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004China The moe key laboratory of biosystems homeostasis&protection and Innovation Centerfor cell Signaling Network Life Sciences InstituteZhejiang UniversityHangzhou 310058China zhejiang provincial key Lab of Geriatrics and Geriatrics Institute of zhejiang Province Department of GeriatricsZhejiang Hospital.Hangzhou310030China Trauma Center The First Afiliated HospitalZhejiang University School of MedicineHangzhou 310003China The Afiliated Hospitalof Stomatology Schoolof StomatologyZhejiang University Schoolof MedicineKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceHangzhou 310006China zhejiang provincial key Labratoryof cancer molecular cell biology Life Sciences InstituteZhejiang UniversityHangzhou 30058China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA.Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors(Canela et al.,2017).Among the various forms of DNA damage,DNA doublestrand breaks(DSBs)are particularly harmful.Two major pathways,non-homologous end joining(NHEJ)and homologous recombination(HR),are primarily responsible for repairing DSBs(Katsuki et al.,2020;Li and Yuan,2021;Zhang and Gong,2021;Xiang et al.,2023).NHEJ is an error-prone repair mechanism that simply joins the broken ends together(Blunt et al.,1995;Hartley et al.,1995).

关键词： damage homologous

A chromosome minimalist view of genome regulation and evolution based on mouse chromosome engineering

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Zoological Research 2022年第6期43卷 949-951页

作者： Qi Zhou moe laboratory of biosystems homeostasis and protection and zhejiang provincial key laboratory for cancer molecular cell biology Life Sciences InstituteZhejiang UniversityHangzhouZhejiang 310058China Center for Reproductive Medicine 2nd Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310052China Evolutionary&Organismal biology Research Center School of MedicineZhejiang UniversityHangzhouZhejiang 310058China

What is the minimum number of chromosomes that a eukaryotic species can tolerate?This question has long fascinated biologists as chromosomal rearrangements are associated with both speciation and various genetic diseases.Nature already has an answer,at least for mammals.In the 1970s,researchers at the Kunming Institute of Zoology(KIZ)。

关键词： evolution Kunming chromosome

Role of pyroptosis in inflammation and cancer

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cellular & molecular Immunology 2022年第9期19卷 971-992页

作者： Xiang Wei Feng Xie Xiaoxue Zhou Yuchen Wu Haiyan Yan Ting Liu Jun Huang Fangwei Wang Fangfang Zhou Long Zhang International Biomed-X Research Center Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang310058PR China Institutes of biology and Medical Science Soochow UniversitySuzhou215123PR China moe key laboratory of biosystems homeostasis&protection and Innovation Center for cell Signaling Network Life Sciences InstituteZhejiang UniversityHangzhouZhejiang310058PR China Department of Clinical Medicine The First School of MedicineWenzhou Medical UniversityWenzhouZhejiang325035PR China School of Medicine Zhejiang University City CollegeHangzhouZhejiang310015PR China Department of cell biology and Department of General Surgery of Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou310058ZhejiangPR China zhejiang provincial key Lab of Geriatrics and Geriatrics Institute of zhejiang Province Department of GeriatricsZhejiang HospitalHangzhouZhejiang310030PR China zhejiang provincial key laboratory of cancer molecular cell biology Life Sciences InstituteZhejiang UniversityHangzhouZhejiang310058PR China

Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.

关键词： Pyroptosis inflammasome influencing factors pyroptosis-associated diseases antitumor targeted therapy