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撤稿:Tip60-foxo调节果蝇JNK信号通路介导的细胞凋亡[遗传,2024,46(6):490-501]

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遗传 2024年第7期46卷 586-586页

作者：杨剑石国娟彭昂惠徐清波王睿琪薛雷喻昕阳孙艺昊不详

发表于《遗传》2024年第6期的文章“Tip60-foxo调节果蝇JNK信号通路介导的细胞凋亡”(作者:杨剑,石国娟,彭昂惠,徐清波,王睿琪,薛雷,喻昕阳,孙艺昊),因作者实验室近期发现部分在该文章中使用的果蝇品系出现了污染,导致实验结果不稳定,... 详细信息

发表于《遗传》2024年第6期的文章“Tip60-foxo调节果蝇JNK信号通路介导的细胞凋亡”(作者:杨剑,石国娟,彭昂惠,徐清波,王睿琪,薛雷,喻昕阳,孙艺昊),因作者实验室近期发现部分在该文章中使用的果蝇品系出现了污染,导致实验结果不稳定,无法完全重复该文章中的结果。为严谨起见,文章所有作者一致申请撤稿并表示歉意。

关键词： JNK信号通路细胞凋亡 foxo 撤稿果蝇

foxo is required for optimal fitness of the migratory brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae)

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Insect Science 2023年第5期30卷 1352-1362页

作者： Jin-Li Zhang Ke-Liang Liu Xin-Yu Cai Xin-Yang Liu Hai-Jun Xu State Key Laboratory of Rice Biology Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang ProvinceInstitute of Insect SciencesCollege of Agriculture and BiotechnologyZhejiang UniversityHangzhouChina

The forkhead box O(foxo)protein is the main transcriptional effector downstream of the insulin/insulin-like signaling pathway and regulates many developmental and physiological *** insects with loss-of-function mutations in foxo exhibit phenotypes distinct from those of hemimetabolous insects in which RNA interference was *** the functional importance of foxo,whether hemimetabolous insects share an evolutionally conserved function of foxo with holometabolous insects remains to be *** used the clustered regularly interspaced short palindromic repeats/CRISPR-associated 9(CRISPR/Cas9)genome editing-system to establish a homozygous foxo-null mutant(Nlfoxo^(4E))of the wing-dimorphic brown planthopper(BPH)Nilaparvata lugens,an economically important insect pest of rice *** phenotypes of Nlfoxo^(4E) mutants included extended nymphal duration,shortened lifespan,reduced reproduction,and decreased stress *** addition,depletion of Nlfoxo promoted cell proliferation in wing buds and led to 100%long-winged morphs,in stark contrast to short-winged wild-type *** findings indicate that Nlfoxo is highly functionally conserved with its counterpart in holometabolous insects,and is required for optimal fitness of *** insights from foxo studies may facilitate the identification of potential target genes for BPH control applications.

关键词： cell proliferation CRISPR/Cas9 foxo longevity planthopper reproduction

MicroRNA miR-2765-3p regulates reproductive diapause by targeting foxo in Galeruca daurica

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Insect Science 2023年第2期30卷 279-292页

作者： Tian-Feng Duan Ling Li Hai-Chao Wang Bao-Ping Pang Research Center for Grassland Entomology Inner Mongolia Agricultural UniversityHohhotChina

The forkhead box O(foxo),as a conserved transcription factor,plays an indispensable role in regulating insect ***,how foxo is regulated to control diapause in insects remains *** this study,we discovered functional binding sites for miR-2765-3p in the 3′untranslated region of foxo in Galeruca *** luciferase reporter assay showed that miR-2765-3p targeted foxo and suppressed its *** expression profiles of miR-2765-3p and foxo displayed opposite patterns during the female developmental *** of miR-2765-3p by the injection of the miR-2765-3p agomir into adult females reduced foxo expression,leading to the suppression of lipid accumulation,promotion of ovarian development,and inhibition of reproductive *** is similar to the phenotype that results from the depletion of foxo by injecting dsfoxo into adult *** addition,the repression of miR-2765-3p by injecting the miR-2765-3p antagomir increased the foxo transcript level,leading to the stimulation of lipid accumulation,depression of ovarian development,and induction of reproductive diapause.A hormone injection assay showed that the juvenile hormone(JH)agonist(methoprene)upregulated miR-2765-3p and downregulated ***,injecting methoprene rescued ovarian development defects associated with miR-2765-3p *** findings indicate that the JH/miR-2765-3p/foxo axis plays a vital role in the regulation of reproductive diapause in ***.

关键词： diapause foxo Galeruca daurica juvenile hormone microRNA

foxo directly regulates the expression of TOR/S6K and vitellogenin to modulate the fecundity of the brown planthopper

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Science China(Life Sciences) 2021年第1期64卷 133-143页

作者： Yi Dong Weiwen Chen Kui Kang Rui Pang Yipei Dong Kai Liu Wenqing Zhang State Key Laboratory of Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou510275China

As a conserved transcription factor,foxo plays a crucial role in multiple physiological processes in vivo,including stress resistance,longevity,growth and *** studies on foxo have focused on human,mouse,Drosophila melanogaster and Caenorhabditis elegans,while there are few reports on agricultural pests and little is known about how foxo modulates insect *** Asia,the brown planthopper(BPH)Nilaparvata lugens(St?l)is one of the most serious pests in rice production and high fecundity is the basis of the outbreak of ***,using the genome-wide ChIP-seq of Nlfoxo in BPH,we found that Nlfoxo binds to the promoters of ribosomal protein S6 kinase(NlS6K)and serine/threonine-protein kinase mTOR(NlTOR)and increases their expression *** also found that Nlfoxo directly binds to the exon of vitellogenin(NlVg)and has a specific inhibitory effect on its *** addition,the number of eggs laid and their hatching rate decreased significantly after injection of Nlfoxo double-stranded RNA into BPH *** findings provide direct evidence that foxo modulates insect fecundity through binding to the promoters of NlS6K,NlTOR and the exon of NlVg and affecting their gene expression in the Vg network.

关键词： foxo ChIP-seq Nilaparvata lugens fecundity vitellogenin(Vg) bind

Applications of post-translational modifications of foxo family proteins in biological functions

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分子细胞生物学报:英文版 2011年第5期3卷 276-282页

作者： Ying Zhao Yachen Wang Wei-Guo Zhu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Biochemistry and Molecular BiologyPeking University Health Science CenterBeijing 100191China School of Oncology Peking University Health Science CenterBeijing 100191China

The functions of the foxo family proteins,in particular their transcriptional activities,are modulated by post-translational modifi-cations(PTMs),including phosphorylation,acetylation,ubiquitination,methylation and *** PTMs occur in response to different cellular stresses,which in turn regulate the subcellular localization of foxo family proteins,as well as their half-life,DNA binding,transcriptional activity and ability to interact with other cellular *** this review,we summarize the role of PTMs of foxo family proteins in linking their biological and functional relevance with various diseases.

关键词： foxo post-translational modification cancer

Targeting the core of neurodegeneration:foxo,mTOR,and SIRT1

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Neural Regeneration Research 2021年第3期16卷 448-455页

作者： Kenneth Maiese Cellular and Molecular Signaling New York New YorkNYUSA

The global increase in lifespan noted not only in developed nations,but also in large developing countries parallels an observed increase in a significant number of noncommunicable diseases,most notable neurodegenerative *** disorders present a number of challenges for treatment options that do not resolve disease ***,it is believed by the year 2030,the services required to treat cognitive disorders in the United States alone will exceed$2 trillion *** forkhead transcription factors,silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae),the mechanistic target of rapamycin,and the pathways of autophagy and apoptosis offer exciting avenues to address these challenges by focusing upon core cellular mechanisms that may significantly impact nervous system *** pathways are intimately linked such as through cell signaling pathways involving protein kinase B and can foster,sometimes in conjunction with trophic factors,enhanced neuronal survival,reduction in toxic intracellular accumulations,and mitochondrial *** mechanisms among these pathways also exist that can oversee reparative processes in the nervous ***,mammalian forkhead transcription factors,silent mating type information regulation 2 homolog 1,mechanistic target of rapamycin,and autophagy can lead to cellular demise under some scenarios that may be dependent upon the precise cellular environment,warranting future studies to effectively translate these core pathways into successful clinical treatment strategies for neurodegenerative disorders.

关键词： Alzheimer's disease apoptosis autophagy erythropoietin forkhead foxo mechanistic target of rapamycin silent mating type information regulation 2 homolog 1

赤拟谷盗胞质磺基转移酶功能及上游foxo和CncC-Keap1通路调控关系研究

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赤拟谷盗胞质磺基转移酶功能及上游FOXO和CncC-Keap1通路调控关系...

作者：徐鑫扬州大学

学位级别：硕士

磺基转移酶（sulfotransferase,SULT）是磺基转移酶超家族成员,通过催化磺酸基供体化合物3’-磷酸腺苷-5’-磷酰硫酸（PAPS）上的磺酸基团（SO3-）转移至特定底物上的羟基或氨基上以形成水溶性更强的硫酸酯类化合物从而更好地排出体外... 详细信息

磺基转移酶（sulfotransferase,SULT）是磺基转移酶超家族成员,通过催化磺酸基供体化合物3’-磷酸腺苷-5’-磷酰硫酸（PAPS）上的磺酸基团（SO3-）转移至特定底物上的羟基或氨基上以形成水溶性更强的硫酸酯类化合物从而更好地排出体外。根据亚细胞定位将磺基转移酶分为胞质磺基转移酶（cytosolic SULTs）以及膜偶联磺基转移酶（membrane-associated,SULTs）。磺基转移酶在动植物以及微生物中高度保守并且具有广泛的底物多样性,在维持生物体稳态和调节生物体代谢等方面发挥着重要作用。本文以重要仓储害虫赤拟谷盗（Tribolium castaneum）作为研究材料,在克隆6个赤拟谷盗胞质磺基转移酶基因的基础上,对其组织表达模式、解毒代谢功能、表达调控机制及其上游foxo和CncC-Keap1通路调控关系进行分析。从赤拟谷盗转录组中检索得到了 6个胞质磺基转移酶基因TcSULT1-6,通过RT-PCR获得了这6个胞质磺基转移酶基因的开放阅读框（Open Reading Frame,ORF）序列。赤拟谷盗胞质磺基转移酶基因ORF长度在957 bp（TcSULT1）～1095 bp（TcSULT6）之间,编码318～364个氨基酸。分子质量在37.40 kDa（TcSULT3）～43.28 kDa（TcSULT6）之间,等电点在 5.89（TcSULT4）～8.18（TcSULT3）之间。氨基酸序列比对发现TcSULTs具有保守的SULT特征性基序（N-YPK（A/S）GTxW,C-RKGxxGDW（V/K）NxFT）,系统发生分析也显示TcSULTs与其他昆虫SULTs同源。利用实时荧光定量PCR（RT-qPCR）分析TcSULTs在赤拟谷盗7日龄成虫不同组织中的表达情况,发现TcSULT2的mRNA表达水平在马氏管中最高,在脂肪体中最低;TcSULT3的mRNA表达水平在马氏管中最高,在卵巢中最低;TcSULT5的mRNA表达水平在卵巢中最高,在头部最低;TcSULT6的mRNA表达水平在头部最高,在卵巢中最低;而TcSULT1和TcSULT4在各组织中表达水平都很低。利用RT-qPCR检测了 LC50（5.87 mg/L）溴氰菊酯对TcSULTs的诱导作用,结果显示与对照组相比,TcSULT2表达水平在溴氰菊酯处理2 h时显著上调了3.69倍;TcSULT3表达水平在2h时上调倍数最高,达到了 9.95倍,其余各时间段也均显著上调;TcSULT5表达水平在2 h及4 h时分别显著上调了 2.58倍和2.35倍;TcSULT6表达水平在1h时先是下调了 56%,后在4 h时又显著上调了 1.81倍。进一步利用RNA干扰（RNA interference,RNAi）技术研究发现,赤拟谷盗4日龄雌蛹中注射了 dsTcSULTs 6天后,TcSULT2、3、5和6的mRNA表达水平分别显著下调了 84.3%,95%,81.7%和87.7%,并且TcSULTs敲减后的赤拟谷盗显示出对溴氰菊酯更高的敏感性。这些结果表明TcSULTs可以响应溴氰菊酯的诱导,并且可能在赤拟谷盗对溴氰菊酯解毒代谢过程中发挥重要作用。利用RNAi技术、RT-qPCR和双荧光素酶报告基因分析探究TcCncC对TcSULTs的表达调控。首先在15日龄幼虫中敲减了 TcCncC,在注射后第6天时TcCncC的mRNA表达水平显著下调了 51%。TcCncC敲减使得TcSULT3和6的mRNA表达水平分别显著下调了 36.7%和60.7%,而TcSULT5 mRNA表达水平上调至对照组的69.8倍。双荧光素酶报告基因分析显示TcCncC以及TcMaf在草地贪夜蛾（Spodoptera frugiperda）Sf9细胞中共表达时使得TcSUL T3和TcSULT6的启动子活性分别上调至对照组的2.71倍和2.15倍,使得TcSULT5的启动子活性显著下调了 70.57%。这些结果表明TcCncC可以结合TcSULT3、5和6的启动子区域直接调控它们的表达。利用RNAi和RT-qPCR研究Tcfoxo在外源化合物代谢中的作用。Tcfoxo敲减使得TcSULT3和TcSUL T6的mRNA表达水平分别显著降低了 50.3%和33%,并且引起赤拟谷盗对溴氰菊酯敏感性的上升。这一结果表明Tcfoxo可能通过调节TcSULT3和TcSUL T6的表达来参与溴氰菊酯解毒代谢。利用RT-qPCR、RNAi、双荧光素酶报告基因分析和凝胶阻滞实验（Electrophoretic mobility shift assay,EMSA）探讨 foxo 以及 CncC-Keap1 信号通路间的调控关系。Tcfoxo敲减显著降低了 TcCncC和TcKeap1的mR

关键词：胞质磺基转移酶 foxo CncC-Keap1 解毒调控机制

Polymorphisms in the foxo gene are associated with growth traits in the Sanmen breeding population of the razor clam Sinonovacula constricta

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Aquaculture and Fisheries 2018年第5期3卷 177-183页

作者： Shumei Xie Donghong Niu Kanyun Wei Zhiguo Dong Jiale Li Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources Ministry of EducationShanghai Ocean UniversityShanghai201306China National Demonstration Center for Experimental Fisheries Science Education Shanghai Ocean UniversityShanghai201306China Shanghai Engineering Research Center of Aquaculture Shanghai201306China Co-Innovation Center of Jiangsu Marine Bio-industry Technology Lianyungang222001China

We identified the foxo gene and five single-nucleotide polymorphisms(SNPs)in its coding region in the Sanmen breeding population of the razor clam Sinonovacula *** Scfoxo gene encodes a protein of 625 amino acids in length that contains a conserved DNA-binding ***-time polymerase chain reaction analysis showed that Scfoxo mRNA is widely expressed in adult tissues,with higher expression in the siphons and *** the SNPs,c.879G>C(Val293Val)and c.1725A>G(Ser575Ser)are synonymous mutations,and c.543C>T(Phe181Leu),c.848A>G(Tyr283Cys),and c.1625G>C(Gly542Phe)are non-synonymous *** SNPs all show significant associations with total body weight,shell length,shell width,and shell height(SH)in this *** parameter analysis showed that all SNPs except c.848A>G(Tyr283Cys)exhibit complete *** SNP c.1625G>C(Gly542Phe)was used for genetic linkage mapping and demonstrates the strongest linkage(logarithm of the odds[LOD]value:41.46)with the marker 96616(37.02 cM)in the linkage group *** LOD value of this marker in relation to growth traits ranges from 1.04 to 1.53;only markers with a LOD value3 were considered to be linked with growth traits in the razor clam linkage *** summary,Scfoxo may be a growth trait-related gene and may represent a marker for Sanmen breeding group selection.

关键词： Sinonovacula constricta Single-nucleotide polymorphism(SNP) foxo Growth traits

Diverse roles of foxo family members in gastric cancer

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1367-1382页

作者： Yu-Han Chen Chun-Lan Li Wen-Jia Chen Jing Liu Hua-Tao Wu Department of Clinical Medicine Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer Changjiang Scholar's LaboratoryDepartment of PhysiologyShantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of General Surgery The First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

Gastric cancer(GC)is the fifth most diagnosed cancer and the third leading causeof cancer-related death *** progress has been made in diagnosis,surgical resection,systemic chemotherapy,and immunotherapy,patientswith GC still have a poor *** overall 5-year survival rate in patientswith advanced GC is less than 5%.The foxo subfamily,of the forkhead boxfamily of transcription factors,consists of four members,foxo1,foxo3,foxo4,and *** subfamily plays an important role in many cellular processes,such as cell cycle,cell growth,apoptosis,autophagy,stress resistance,protectionfrom aggregate toxicity,DNA repair,tumor suppression,and metabolism,in bothnormal tissue and malignant *** studies support a role for foxos astumor suppressors based on their ability to inhibit angiogenesis and metastasis,and promote apoptosis,yet several other studies have shown that foxos mightalso promote tumor progression in certain *** elucidate the diverseroles of foxos in GC,this article systematically reviews the cellular functions offoxos in GC to determine potential therapeutic targets and treatment strategiesfor patients with GC.

关键词： foxo Gastric cancer Regulation Therapy Expression