本文旨在对3个影响猪达100 kg体重日龄(Age at 100 kg,AGE)和达100 kg体重平均日增重(Average Daily Gain at 100 kg,ADG)的候选基因进行生物信息学分析。运用生物信息学数据库及其软件,分别分析了肉碱O-乙酰转移酶(Carnitine O-acetylt...本文旨在对3个影响猪达100 kg体重日龄(Age at 100 kg,AGE)和达100 kg体重平均日增重(Average Daily Gain at 100 kg,ADG)的候选基因进行生物信息学分析。运用生物信息学数据库及其软件,分别分析了肉碱O-乙酰转移酶(Carnitine O-acetyltransferase,CRAT)、G蛋白偶联受体107(G Protein-Coupled Receptor 107,GPR107)和泛素特异性肽酶20(Ubiquitin Specific Peptidase 20,USP20)3个基因与其编码的产物。结果发现:CRAT基因位于猪的1号染色体,具有15个外显子、14个内含子,共编码626个氨基酸;USP20基因位于猪的1号染色体,具有26个外显子,25个内含子,共编码915个氨基酸;GPR107基因位于猪的1号染色体,具有19个外显子、18个内含子,共编码597个氨基酸;3个蛋白的二级结构主要组成均为无规则卷曲,且均表现出疏水特征,含有磷酸化位点,仅GPR107蛋白检测到信号肽和跨膜结构;猪CRAT、USP20、GPR107在进化过程中与其他哺乳动物之间均具有高度保守性以及序列同源性;CRAT与羟基类固醇17-β脱氢酶4(Hydroxysteroid 17-Beta Dehydrogenase 4,HSD17B4)、囊泡乙酰胆碱转运蛋白(Solute Carrier Family 18 Member A3,SLC18A3)、脂肪酶(Patatin Like Phospholipase Domain Containing 2,PNPLA2)等蛋白互作;USP20与STAM结合蛋白样1(STAM Binding Protein Like 1,STAMBPL1)、β2-肾上腺素能受体(Adrenoceptor Beta 2,ADRB2)、泛素特异性肽酶14(Ubiquitin Specific Peptidase 14,USP14)等蛋白互作;GPR107与LIN52(Lin-52 Homolog,LIN52)、P-选择素(Selectin P,SELP)、G蛋白偶联受体137C(G Protein-Coupled Receptor 137C,GPR137C)等蛋白互作;GO富集分析发现CRAT、USP20、GPR107主要参与脂肪酸的分解代谢、蛋白质稳定性和降解、配子生成过程;CRAT基因在肌肉组织中高表达,USP20基因在下丘脑中高表达,GPR107基因在血管和下丘脑中高表达。本文结果为进一步研究猪生长性状相关的功能基因提供了数据与理论参考。展开更多
T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive hematologic malignancy with a poor prognosis,despite advancements in treatment.Many patients struggle with relapse or refrac-tory disease.Investigating ...T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive hematologic malignancy with a poor prognosis,despite advancements in treatment.Many patients struggle with relapse or refrac-tory disease.Investigating the role of the super-enhancer(SE)regulated gene ubiquitin-specific protease 20(USP20)in T-ALL could enhance targeted therapies and improve clinical outcomes.Analysis of his-tone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation sequencing(ChIP-seq)data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene.Utilizing the Cancer Cell Line Encyclopedia(CCLE)and BloodSpot databases,it was found that USP20 is specifically highly expressed in T-ALL.Knocking down USP20 with short hairpin RNA(shRNA)increased apoptosis and inhibited proliferation in T-ALL cells.In vivo studies showed that USP20 knock-down reduced tumor growth and improved survival.The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects.Mass spectrometry,RNA-Seq,and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha(HIF1A)and stabilized it by deubiquitination.Cleavage under targets and tagmentation(CUT&Tag)results indicated that USP20 co-localized with HIF1A,jointly modulating target genes in T-ALL.This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.展开更多
Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identi...Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.展开更多
文摘本文旨在对3个影响猪达100 kg体重日龄(Age at 100 kg,AGE)和达100 kg体重平均日增重(Average Daily Gain at 100 kg,ADG)的候选基因进行生物信息学分析。运用生物信息学数据库及其软件,分别分析了肉碱O-乙酰转移酶(Carnitine O-acetyltransferase,CRAT)、G蛋白偶联受体107(G Protein-Coupled Receptor 107,GPR107)和泛素特异性肽酶20(Ubiquitin Specific Peptidase 20,USP20)3个基因与其编码的产物。结果发现:CRAT基因位于猪的1号染色体,具有15个外显子、14个内含子,共编码626个氨基酸;USP20基因位于猪的1号染色体,具有26个外显子,25个内含子,共编码915个氨基酸;GPR107基因位于猪的1号染色体,具有19个外显子、18个内含子,共编码597个氨基酸;3个蛋白的二级结构主要组成均为无规则卷曲,且均表现出疏水特征,含有磷酸化位点,仅GPR107蛋白检测到信号肽和跨膜结构;猪CRAT、USP20、GPR107在进化过程中与其他哺乳动物之间均具有高度保守性以及序列同源性;CRAT与羟基类固醇17-β脱氢酶4(Hydroxysteroid 17-Beta Dehydrogenase 4,HSD17B4)、囊泡乙酰胆碱转运蛋白(Solute Carrier Family 18 Member A3,SLC18A3)、脂肪酶(Patatin Like Phospholipase Domain Containing 2,PNPLA2)等蛋白互作;USP20与STAM结合蛋白样1(STAM Binding Protein Like 1,STAMBPL1)、β2-肾上腺素能受体(Adrenoceptor Beta 2,ADRB2)、泛素特异性肽酶14(Ubiquitin Specific Peptidase 14,USP14)等蛋白互作;GPR107与LIN52(Lin-52 Homolog,LIN52)、P-选择素(Selectin P,SELP)、G蛋白偶联受体137C(G Protein-Coupled Receptor 137C,GPR137C)等蛋白互作;GO富集分析发现CRAT、USP20、GPR107主要参与脂肪酸的分解代谢、蛋白质稳定性和降解、配子生成过程;CRAT基因在肌肉组织中高表达,USP20基因在下丘脑中高表达,GPR107基因在血管和下丘脑中高表达。本文结果为进一步研究猪生长性状相关的功能基因提供了数据与理论参考。
基金supported by grants from the National Key R&D Program of China(2022YFC2502700)National Natural Science Foundation(82072767,82141110,82172840,82203442,82300182,and 82373414,China)+5 种基金Natural Science Foundation of Jiangsu Province(BK20220047,China)Jiangsu Province’s Science and Technology Support Program(Social Development)project(BE2021657 and BE2022732,China)Suzhou Health Talent Training Project(GSWS2020047,GSWS2021028 and GSWS2022062,China)the Science and Technology Development Project of Suzhou City(SKY2022170 and SKY2023192,China)Jiangsu Provincial Health Commission Scientific Research Project(Z2022031,M2022102,ZD2022056 and H2023106,China)Medical Research Project of Jiangsu Provincial Health and Family Planning Commission(Key Project ZD2021006,China)and National Outstanding Youth Cultivation Program Project(YYJQ004,China).
文摘T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive hematologic malignancy with a poor prognosis,despite advancements in treatment.Many patients struggle with relapse or refrac-tory disease.Investigating the role of the super-enhancer(SE)regulated gene ubiquitin-specific protease 20(USP20)in T-ALL could enhance targeted therapies and improve clinical outcomes.Analysis of his-tone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation sequencing(ChIP-seq)data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene.Utilizing the Cancer Cell Line Encyclopedia(CCLE)and BloodSpot databases,it was found that USP20 is specifically highly expressed in T-ALL.Knocking down USP20 with short hairpin RNA(shRNA)increased apoptosis and inhibited proliferation in T-ALL cells.In vivo studies showed that USP20 knock-down reduced tumor growth and improved survival.The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects.Mass spectrometry,RNA-Seq,and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha(HIF1A)and stabilized it by deubiquitination.Cleavage under targets and tagmentation(CUT&Tag)results indicated that USP20 co-localized with HIF1A,jointly modulating target genes in T-ALL.This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
基金supported by the National Natural Science Foundation of China(31620103917 31970459 32070441 31702054 and 31930014)the Shenzhen Science and Technology Program(20180411143628272)the Natural Science Foundation of Guangdong Province(2019A1515011899)。
文摘Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.
