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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
《工程(英文)》 2024年 第32卷 第1期 页码 58-69 doi: 10.1016/j.eng.2023.09.019
Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
关键词: Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells
Protein phosphatase 2A, a key player in Alzheimer’s disease
Rong LIU, Qing TIAN
《医学前沿(英文)》 2009年 第3卷 第1期 页码 8-12 doi: 10.1007/s11684-009-0017-6
关键词: protein phosphatase 2A Alzheimer’s disease holoenzyme composition protein phosphatase 2A inhibitors Leu309 demethylation Tyr307 phosphorylation
吴剑,王世和
《中国工程科学》 2007年 第9卷 第11期 页码 191-195
为开发高效除磷脱氮技术,研制了将MBR与A2/O工艺有机集成的新型MB(A2/O)组合工艺。研究 了MB(A2/O)工艺处理城市污水的好氧、缺氧摄磷性能及微生物特性,并分析了其机理。结果表明:在 MB(A2/O)系统中,聚磷菌约占活性污泥总量的20%~40%,其中大量存在能够利用NOX-N作为电子受体 进行反硝化除磷的DPB,约占聚磷菌数量的35. 66%~67好氧摄磷的平均速率为2. 30mgP·gMLSS-1·h-1,最大摄磷速率为5. 44mgP·gMLSS-
Dual faces of SH2-containing protein-tyrosine phosphatase
null
《医学前沿(英文)》 2012年 第6卷 第3期 页码 275-279 doi: 10.1007/s11684-012-0216-4
PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Against original prediction as tumor suppressor for tyrosine phosphatases, PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis. However, most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis. This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.
Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine
Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,
《医学前沿(英文)》 2009年 第3卷 第4期 页码 390-395 doi: 10.1007/s11684-009-0087-5
关键词: Epstein-Barr virus latent membrane protein 2 nasopharyngeal carcinoma humoral immunity
LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing
《医学前沿(英文)》 2008年 第2卷 第3期 页码 235-238 doi: 10.1007/s11684-008-0044-8
关键词: hyperphosphorylation PP2A activity cellular regulation siRNA siRNA transfection
Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages
LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao
《医学前沿(英文)》 2008年 第2卷 第2期 页码 166-170 doi: 10.1007/s11684-008-0030-1
Genetic association between the polymorphism of cytosolic PLA2 gene family and schizophrenia
Qiong YU PhD, Xiang-Fei MENG PhD, Jie-Ping SHI, Ya-Qin YU PhD,
《医学前沿(英文)》 2010年 第4卷 第1期 页码 101-105 doi: 10.1007/s11684-010-0017-6
关键词: schizophrenia cytosolic phospholipase A2 ligase detection reaction polymorphism
null
《医学前沿(英文)》 2017年 第11卷 第3期 页码 410-422 doi: 10.1007/s11684-017-0527-6
Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor a (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5′-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29±0.13 fold higher than that by control pSG5 vector or wild-type RARα. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.
关键词: annexin A2-S100A10 heterotetramer PML/RARα fusion protein plasmin cell invasion acute promyelocytic leukemia
XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing
《医学前沿(英文)》 2007年 第1卷 第2期 页码 200-206 doi: 10.1007/s11684-007-0038-y
Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,
《医学前沿(英文)》 2009年 第3卷 第3期 页码 309-315 doi: 10.1007/s11684-009-0043-4
关键词: graft vs host disease proteinase-activated receptor murine model hematopoietic stem cell transplantation
Mechanisms of insulin resistance in obesity
null
《医学前沿(英文)》 2013年 第7卷 第1期 页码 14-24 doi: 10.1007/s11684-013-0262-6
Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that, there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.
关键词: type 2 diabetes energy expenditure inflammation lipotoxicity mitochondria hyperinsulinemia adenosine monophosphate-activated protein kinase (AMPK)
新型冠状病毒HCoV-19 S蛋白与人ACE2蛋白表面糖链和独特翻译后修饰的质谱分析 Article
孙泽宇, 任科燚, 张兴, 陈景华, 姜正一, 江静, 季飞洋, 欧阳晓希, 李兰娟
《工程(英文)》 2021年 第7卷 第10期 页码 1441-1451 doi: 10.1016/j.eng.2020.07.014
作为免疫疗法靶点的FOXP3及其辅因子 Review
Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang
《工程(英文)》 2019年 第5卷 第1期 页码 115-121 doi: 10.1016/j.eng.2019.01.001
叉头框蛋白P3(FOXP3)是调节性T细胞(Tregs)的一个主要调节因子,调节性T细胞是能抑制抗原特异性免疫反应的T 细胞亚群,在增强宿主耐受性和维持免疫平衡方面发挥着重要作用。众所周知,FOXP3 与多种蛋白质形成复合物,并能通过乙酰化、磷酸化、泛素化和甲基化等各种翻译后修饰(PTM)进行调节。因此,翻译后修饰可改变FOXP3 的稳定性及其调节基因表达的能力,并最终影响调节性T细胞活性。虽然FOXP3 自身并非理想的药物靶点,但脱乙酰酶、乙酰转移酶、激酶和其他可调节FOXP3 的翻译后修饰的酶均为调控FOXP3 和调节性T细胞活性的潜在靶点。但FOXP3 并非这些酶的唯一底物;因此,当使用相关抑制剂时,必须考虑是否存在有害的“FOXP3脱靶”副作用。在本文中,我们总结了有关FOXP3 辅助因子和蛋白质翻译后修饰的最新研究进展,以及它们在自体免疫和癌症免疫中的潜在临床应用。
关键词: 调节性T细胞 叉头框蛋白P3(FOXP3) 翻译后修饰 自体免疫 癌症
Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance
null
《医学前沿(英文)》 2012年 第6卷 第4期 页码 376-380 doi: 10.1007/s11684-012-0228-0
The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.
关键词: FOXO3a FOXM1 transcription factor cancer drug resistance tumorigenesis
标题 作者 时间 类型 操作
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
期刊论文
Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine
Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,
期刊论文
Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation
LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing
期刊论文
Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages
LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao
期刊论文
Genetic association between the polymorphism of cytosolic PLA2 gene family and schizophrenia
Qiong YU PhD, Xiang-Fei MENG PhD, Jie-Ping SHI, Ya-Qin YU PhD,
期刊论文
Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent
null
期刊论文
Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive
XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing
期刊论文
Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host
Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,
期刊论文