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PGK1-coupled HSP90 stabilizes GSK3βexpression to regulate the stemness of breast cancer stem cells

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Cancer Biology & Medicine 2022年第4期19卷 486-503页

作者： Wei Tang Yu Wu Xin Qi Rilei Yu zhimin lu Ao Chen Xinglong Fan Jing Li Key Laboratory of Marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease of the First Affiliated Hospital Institute of Translational MedicineZhejiang UniversityHangzhou 310029China Department of Thoracic Surgery Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266003China Open Studio for Druggability Research of Marine Natural Products Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266003China Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology Qingdao 266003China

Objective:Glycogen synthase kinase-3β(GSK3β)has been recognized as a suppressor of Wnt/β-catenin signaling,which is critical for the stemness maintenance of breast cancer stem ***,the regulatory mechanisms of GSK3βprotein expression remain ***:Co-immunoprecipitation and mass spectral assays were performed to identify molecules binding to GSK3β,and to characterize the interactions of GSK3β,heat shock protein 90(Hsp90),and *** role of PGK1 in Hsp90 chaperoning GSK3βwas evaluated by constructing 293T cells stably expressing different domains/mutants of Hsp90α,and by performing a series of binding assays with bacterially purified proteins and clinical *** influences of Hsp90 inhibitors on breast cancer stem cell stemness were investigated by Western blot and mammosphere formation ***:We showed that GSK3βwas a client protein of ***90,which did not directly bind to GSK3β,interacted with phosphoglycerate kinase 1 via its C-terminal domain,thereby facilitating the binding of GSK3βto ***3β-bound PGK1 interacted with Hsp90 in the“closed”conformation and stabilized GSK3βexpression in an Hsp90 activity-dependent *** Hsp90 inhibitor,17-AAG,rather than HDN-1,disrupted the interaction between Hsp90 and PGK1,and reduced GSK3βexpression,resulting in significantly reduced inhibition ofβ-catenin expression,to maintain the stemness of breast cancer stem ***:Our findings identified a novel regulatory mechanism of GSK3βexpression involving metabolic enzyme PGK1-coupled Hsp90,and highlighted the potential for more effective cancer treatment by selecting Hsp90 inhibitors that do not affect PGK1-regulated GSK3βexpression.

关键词： Glycogen synthase kinase-3β(GSK3β) heat shock protein 90(Hsp90) phosphoglycerate kinase 1(PGK1) hsp90 inhibitors breast cancer stem cell

Aerobic glycolysis promotes tumor immune evasion and tumor cell stemness through the noncanonical function of hexokinase 2

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Cancer Communications 2023年第3期43卷 387-390页

作者： Haiyan He Liwei Xiao Juhong Wang Dong Guo zhimin lu Department of Pharmacy Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated Hospitaland Institute of Translational MedicineZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Cancer Center Zhejiang UniversityHangzhouZhejiangP.R.China Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China

The Warburg effect is a key metabolic feature of cancer cells and manifests as substantially increased glycolysis regardless of the presence of oxygen[1].The initial step of glycolysis is catalyzed by hexokinase(HK),which converts glucose to the metabolic intermediate glucose-6-phosphate(G-6-P).Four kinds of HK isozymes,HK1,HK2,HK3 and HK4,have been found in ***1 and HK2 bind to the mitochondrial outer membrane through interac-tions with voltage-dependent anion channels(VDACs),and both of thesemolecules have a high affinity for glucose[2].HK2 overexpression is frequently detected in cancer cells,leading to enhanced aerobic glycolysis and tumorigenesis that renders HK2 an attractive target for cancer treatment[3].Important advances in research on cancer metabolism in recent decades have revealed thatmetabolic enzymes have non-metabolic functions,which play pivotal roles in tumor development and progression[4–6].Recent studies uncovered that HK2 directly promoted tumor immune evasion through the activity of a previously unidentified protein kinase and tumor cell stemness via upregulation of CD133 expression.

关键词： glycolysis metabolism attractive

A moonlighting function of choline kinase alpha 2 in the initiation of lipid droplet lipolysis in cancer cells

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Cancer Communications 2021年第10期41卷 933-936页

作者： Qingxia Ma Zhaoyuan Meng Ying Meng Rui Liu zhimin lu Qingdao Cancer Institute The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266071P.R.China Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated HospitalInstitute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310029P.R.China Cancer Center Zhejiang UniversityHangzhouZhejiang 310029P.R.China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesChinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and ManagementWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041P.R.China

Cancer cells in the tumormicroenvironment,where nutrient availability is consistently changing during tumor progression,harness lipid metabolism to support their proliferation,survival,migration,invasion,and metastasis[1].When nutrients in the tumor microenvironment are sufficient,lipids such as triglycerides,steryl esters,and retinyl esters are stored in lipid droplets,which are dynamic lipid-rich cellular organelles surrounded by a single layer of polar and amphipathic phospholipids and structural proteins in the perilipin(PLIN)family.

关键词： metabolism invasion Cancer

Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications

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Research 2023年第2期2023卷 577-581页

作者： Sha Li Nan Li Jie He Runxin Zhou zhimin lu Yizhi Jane Tao Yusong R.Guo Yugang Wang Department of Biochemistry and Molecular Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Neurosurgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Zhejiang University School of Medicine HangzhouZhejiang 310029China Department of Bioscience Rice UniversityHoustonTX 77005USA Cell Architecture Research Center Huazhong University of Science and TechnologyWuhanHubei 430030China

Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases(HATs)advance our understandings in the regulation of histone ***,the molecular basis of HATs selecting acyl coenzyme A(acyl-CoA)substrates for histone modification is less *** here report that lysine acetyltransferase 2A(KAT2A)as an illustrative instance of HATs can selectively utilize acetyl-CoA,propionyl-CoA,butyryl-CoA,and succinyl-CoA to directly deposit 18 histone acylation hallmarks in *** analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA,propionyl-CoA,butyryl-CoA,malonyl-CoA,succinyl-CoA,and glutaryl-CoA,we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by *** study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes,which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells.

关键词： utilize selecting electrostatic

Governing glutaminolysis by regulation of glutaminase succinylation

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Protein & Cell 2022年第3期13卷 163-166页

作者： Qingxia Ma Hongfei Jiang Leina Ma Ying Meng Dong Guo Yingying Tong zhimin lu The Affliated Hospital of Qingdao University Qingdao Cancer InstituteQingdao UniversityQingdao 266071China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospitaland Institute of Translational MedicineZhejiang University School of MedicineZhejiang UniversityHangzhou 310029China Cancer Center Zhejiang UniversityHangzhou 310029China Cancer Center Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China

Of the 20 ribosomally coded amino acid residues,lysine(K)can be frequently and uniquely modified by many types of posttranslational acylation,including acetylation,succinylation,crotonylation,propionylation,butyrylation,glutarylation,malonylation,β-hydroxybutyrylation,and 2-hydroxyisobutyrylation in histones and other proteins(Li et al.,2018a;Xu et al.,2021).Among these acylations,succinylation is a commonly occurred modification,and histone H3K79 succinylation is identified in the transcription start sites of more than 7,000 genes,implying its critical role in the expression regulation of a large number of genes(Wang et al.,2017).Protein succinylation requires the highenergy metabolite,succinyl-coenzyme A(CoA).

关键词： uniquely residues critical

The Warburg effect and beyond

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The Warburg effect and beyond

Study on the physiological indices of Pinus sibirica and Pinus koraiensis seedlings under cold stress

细胞—生命的基础——中国细胞生物学学会2013年全国学术大会·武汉

作者： zhimin lu The University of Texas MD Anderson Cancer Center

Pyruvate kinase M2(PKM2) is highly expressed in multiple cancer types and contributes to the Warburg *** lecture will cover our recent findings on the mechanisms underlying the upregulation of PKM2,nuclear translocation of PKM2,and metabolic and non-metabolic functions of PKM2 in promoting cancer cell metabolism and *** strategic approaches to interrupt

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Journal of Forestry Research 2019年第4期30卷 1255-1265页

作者： Fang Wang Deyang Liang Xiaona Pei Qinhui Zhang Peng Zhang Jianqiu Zhang zhimin lu Yuchun Yang Guifeng Liu Xiyang Zhao State Key Laboratory of Tree Genetics and Breeding Northeast Forestry UniversityHarbin 150040People's Republic of China Jilin Provincial Academy of Forestry Sciences Changchun 136000People's Republic of China

Although Pinus sibirica and Pinus koraiensis are resistant to cold or low temperatures in the cold temperate regions of the northern hemisphere,the former has a stronger cold *** has been limited to the comparison of physiological responses of the two species to cold *** this study,5-year-old seedlings of *** and *** were subjected to six temperature treatments,[20℃(control),0℃,-20℃,-40℃,-60℃,and-80℃],under different stress periods(6,12,24,and 48 h).The results showed that differences in each physiological index were significant between *** and ***,except for the permeability of cell membranes,reactive oxygen species,proline and soluble *** ANOVA test indicated that there were extreme differences among the temperatures for each index,stress time and temperature 9 time for most *** indices showed a similar trend for *** and *** with decreasing temperature or the extension of stress *** sugars and proline increased at 0 to-20℃and then remained unchanged with temperature *** indices showed an increase from 20 to-20℃,stable from-20 to-40℃and a decrease from-40 to-80℃.All the indices increased and then declined along with the prolonged cold stress time,except for the *** 0 to-40℃,the permeability of cell membranes,relative conductivity,reactive oxygen species and malonaldehyde of *** seedlings were higher than in ***,but superoxide dismutase,peroxidase,catalase activity and soluble sugars,proline,and soluble proteins content emerged as *** study compared the physiological mechanism responses to cold stress between *** and *** to provide the basis for the introduction,distribution,and genetic improvement of these coniferous species.

关键词： Pinus sibirica P koraiensis Cold stress Membrane system Antioxidant enzymes

Comparison of genetic impact on growth and wood traits between seedlings and clones from the same plus trees of Pinus koraiensis

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Journal of Forestry Research 2023年第2期34卷 469-480页

作者： Xiaoting Liu zhimin lu Jingui Wu Yuchun Yang Shuchun Li Lin Wu Qingshan Xu Qi Yu Li Zhao Jian Sun Wei Zheng Mulualem Tigabu Xiyang Zhao College of Forestry and Grasslands Jilin Agricultural UniversityChangchun 130118JilinPeople’s Republic of China State Key Laboratory of Tree Genetics and Breeding Northeast Forestry UniversityHarbin 150040HeilongjiangPeople’s Republic of China Jilin Provincial Academy of Forestry Sciences Changchun 130031JilinPeople’s Republic of China lushuihe Forestry Bureau of Jilin Baishan 134506JilinPeople’s Republic of China Forestry Department of Jilin Province Tree Seedling Management StationChangchun 130000JilinPeople’s Republic of China Southern Swedish Forest Research Centre Swedish University of Agricultural SciencesP.O.Box 19023422 LommaSweden

To evaluate the relationships among clones and open pollinated families from the same plus trees and to select elite breeding materials,growth,and wood characteristics of 33-year-old Pinus korainsis clones and families were measured and *** results show that growth and wood characters varied *** variation due to clonal effects was higher than that of family *** ratio of genetic to phenotypic coefficient of variation of clones in growth and wood traits was above 90%,and the repeatability of these characteristics was more than 0.8,whereas the ratio of genetic to phenotypic coefficient of variation of families was above 90%.The broad-sense heritability of all characteristics exceeded 0.4,and the narrow-sense family heritability of growth traits was less than *** characteristics were positively correlated with each other,but most wood properties were weakly correlated in both clones and *** length and width were positively correlated between clones and *** the membership function method,eleven clones and four families were selected as superior material for improved diameter growth and wood production,and two families from clonal and open-pollinated trees showed consistently better ***,selection of the best clones is an effective alternative to deployment of families as the repeatability estimates from clonal trees were higher than narrow-sense heritability estimates from open pollinated *** results provide valuable insight for improving *** breeding programs and subsequent genetic improvement.

关键词： Pinus koraiensis Korean pine Clonal parents Progeny testing Repeatability Broad-sense heritability Narrow-sense heritability

Photonic crystal vertical-cavity surface-emitting laserbased on GaAs material

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Chinese Science Bulletin 2007年第18期52卷 2473-2476页

作者： XU XingSheng WANG ChunXia SONG Qian DU Wei HU HaiYang ZHAO zhimin lu Lin KAN Qiang CHEN HongDa State Key Laboratory of Integrated Optoelectronics Institute of Semiconductor Chinese Academy of Sciences Beijing 100083China

A photonic crystal vertical-cavity-surface-emitting laser (PC-VCSEL) with a wavelength of about 850 nm was realized. The direct-current electrically-driven PC-VCSELs with a minimum threshold current of 2 mA and a maximum threshold current of 13.5 mA were obtained. We fabricated a series of PC-VCSEL chips whose lattice constants are in the range from 0.5 to 3 μm with different filling factors, and found that the laser characterization depends on the lattice constant, the filling factor, the size of cavity, etc.

关键词：光子晶体空穴表面发射激光单模激光砷化镓