13 results on '"Chi, TF"'
Search Results
2. Loss of USF2 promotes proliferation, migration and mitophagy in a redox-dependent manner.
- Author
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Chi TF, Khoder-Agha F, Mennerich D, Kellokumpu S, Miinalainen I, Kietzmann T, and Dimova EY
- Subjects
- Cell Proliferation, Oxidation-Reduction, Promoter Regions, Genetic, Gene Expression Regulation, Mitophagy
- Abstract
The upstream stimulatory factor 2 (USF2) is a transcription factor implicated in several cellular processes and among them, tumor development seems to stand out. However, the data with respect to the role of USF2 in tumor development are conflicting suggesting that it acts either as tumor promoter or suppressor. Here we show that absence of USF2 promotes proliferation and migration. Thereby, we reveal a previously unknown function of USF2 in mitochondrial homeostasis. Mechanistically, we demonstrate that deficiency of USF2 promotes survival by inducing mitophagy in a ROS-sensitive manner by activating both ERK1/2 and AKT. Altogether, this study supports USF2's function as tumor suppressor and highlights its novel role for mitochondrial function and energy homeostasis thereby linking USF2 to conditions such as insulin resistance, type-2 diabetes mellitus, and the metabolic syndrome., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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3. Cyclin-Dependent Kinase 5 (CDK5)-Mediated Phosphorylation of Upstream Stimulatory Factor 2 (USF2) Contributes to Carcinogenesis.
- Author
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Chi TF, Horbach T, Götz C, Kietzmann T, and Dimova EY
- Abstract
The transcription factor USF2 is supposed to have an important role in tumor development. However, the regulatory mechanisms contributing to the function of USF2 are largely unknown. Cyclin-dependent kinase 5 (CDK5) seems to be of importance since high levels of CDK5 were found in different cancers associated with high USF2 expression. Here, we identified USF2 as a phosphorylation target of CDK5. USF2 is phosphorylated by CDK5 at two serine residues, serine 155 and serine 222. Further, phosphorylation of USF2 at these residues was shown to stabilize the protein and to regulate cellular growth and migration. Altogether, these results delineate the importance of the CDK5-USF2 interplay in cancer cells.
- Published
- 2019
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4. The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-1α.
- Author
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Dimova EY, Jakupovic M, Kubaichuk K, Mennerich D, Chi TF, Tamanini F, Oklejewicz M, Hänig J, Byts N, Mäkelä KA, Herzig KH, Koivunen P, Chaves I, van der Horst G, and Kietzmann T
- Abstract
The circadian clock and the hypoxia-signaling pathway are regulated by an integrated interplay of positive and negative feedback limbs that incorporate energy homeostasis and carcinogenesis. We show that the negative circadian regulator CRY1 is also a negative regulator of hypoxia-inducible factor (HIF). Mechanistically, CRY1 interacts with the basic-helix-loop-helix domain of HIF-1α via its tail region. Subsequently, CRY1 reduces HIF-1α half-life and binding of HIFs to target gene promoters. This appeared to be CRY1 specific because genetic disruption of CRY1, but not CRY2, affected the hypoxia response. Furthermore, CRY1 deficiency could induce cellular HIF levels, proliferation, and migration, which could be reversed by CRISPR/Cas9- or short hairpin RNA-mediated HIF knockout. Altogether, our study provides a mechanistic explanation for genetic association studies linking a disruption of the circadian clock with hypoxia-associated processes such as carcinogenesis., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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5. Differential transcriptional regulation of hypoxia-inducible factor-1α by arsenite under normoxia and hypoxia: involvement of Nrf2.
- Author
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Al Taleb Z, Petry A, Chi TF, Mennerich D, Görlach A, Dimova EY, and Kietzmann T
- Subjects
- Animals, Antineoplastic Agents pharmacology, Carcinogens pharmacology, Cell Hypoxia physiology, Cell Line, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases, Fibroblasts drug effects, Fibroblasts metabolism, Heme Oxygenase-1 genetics, Hep G2 Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Mice, NADPH Oxidase 4, NADPH Oxidases, NF-E2-Related Factor 2, Phosphatidylinositol 3-Kinases, Plasminogen Activator Inhibitor 1 genetics, Proto-Oncogene Proteins c-akt, Reactive Oxygen Species metabolism, Arsenites pharmacology, Cell Hypoxia genetics, Gene Expression Regulation drug effects, Hypoxia-Inducible Factor 1, alpha Subunit genetics
- Abstract
Arsenite (As(III)) is widely distributed in nature and can be found in water, food, and air. There is significant evidence that exposure to As(III) is associated with human cancers originated from liver, lung, skin, bladder, kidney, and prostate. Hypoxia plays a role in tumor growth and aggressiveness; adaptation to it is, at least to a large extent, mediated by hypoxia-inducible factor-1α (HIF-1α). In the current study, we investigated As(III) effects on HIF-1α under normoxia and hypoxia in the hepatoma cell line HepG2. We found that As(III) increased HIF-1α protein levels under normoxia while the hypoxia-mediated induction of HIF1α was reduced. Thereby, the As(III) effects on HIF-1α were dependent on both, transcriptional regulation via the transcription factor Nrf2 mediated by NOX4, PI3K/Akt, and ERK1/2 as well as by modulation of HIF-1α protein stability. In line, the different effects of As(III) via participation of HIF-1α and Nrf2 were also seen in tube formation assays with endothelial cells where knockdown of Nrf2 and HIF-1α abolished As(III) effects. Overall, the present study shows that As(III) is a potent inducer of HIF-1α under normoxia but not under hypoxia which may explain, in part, its carcinogenic as well as anti-carcinogenic actions., Key Message: As(III) increased HIF-1α under normoxia but reduced its hypoxia-dependent induction. The As(III) effects on HIF-1α were dependent on ROS, NOX4, PI3K/Akt, and ERK1/2. The As(III) effects under normoxia involved transcriptional regulation via Nrf2. Knockdown of Nrf2 and HIF-1α abolished As(III) effects in tube formation assays. The data may partially explain As(III)'s carcinogenic and anti-carcinogenic actions., Competing Interests: The authors declare that they have no conflict of interest.
- Published
- 2016
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6. Resveratrol: beneficial or not? Opposite effects of resveratrol on hypoxia-dependent PAI-1 expression in tumour and primary cells.
- Author
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Ganjam GK, Chi TF, Kietzmann T, and Dimova EY
- Subjects
- Antineoplastic Agents, Phytogenic therapeutic use, Dose-Response Relationship, Drug, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Hepatocytes metabolism, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Oxygen, Polyphenols chemistry, RNA, Messenger metabolism, Resveratrol, Neoplasms drug therapy, Neoplasms metabolism, Plasminogen Activator Inhibitor 1 metabolism, Stilbenes therapeutic use
- Published
- 2016
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7. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2.
- Author
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Kozlova N, Jensen JK, Chi TF, Samoylenko A, and Kietzmann T
- Subjects
- Animals, Cell Movement, Cell Proliferation, Fibroblasts metabolism, HEK293 Cells, Humans, Low Density Lipoprotein Receptor-Related Protein-1, Mice, RNA, Small Interfering metabolism, Real-Time Polymerase Chain Reaction, Signal Transduction, Transcription, Genetic, Urokinase-Type Plasminogen Activator metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Receptors, LDL metabolism, Serpin E2 metabolism, Tissue Plasminogen Activator metabolism, Tumor Suppressor Proteins metabolism, beta Catenin metabolism
- Abstract
Plasminogen activator inhibitor-1 (PAI-1) is the major and most specific acting urokinase (uPA) and tissue plasminogen activator (tPA) inhibitor. Apart from its function in the fibrinolytic system, PAI-1 was also found to contribute to processes like tissue remodelling, angiogenesis, and tumour progression. However, the role of PAI-1 in those processes remains largely controversial with respect to the influence of PAI-1 on cell signalling pathways. Although PAI-1 does not possess its own cellular receptor, it can be bound to low-density lipoprotein receptor-related protein 1 (LRP1) which was proposed to modulate the β-catenin pathway. Therefore, we used wild-type mouse embryonic fibroblasts (MEFs), and MEFs deficient of LRP1 to study PAI-1 as modulator of the β-catenin pathway. We found that PAI-1 influences MEF proliferation and motility in a LRP1-dependent manner and that β-catenin is important for that response. In addition, expression of β-catenin and β-catenin-dependent transcriptional activity were induced by PAI-1 in wild type MEFs, but not in LRP1-deficient cells. Moreover, PAI-1-induced ERK1/2 activation was more prominent in the LRP1-deficient cells and interestingly knockdown of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels.
- Published
- 2015
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8. GSK3β-dependent phosphorylation alters DNA binding, transactivity and half-life of the transcription factor USF2.
- Author
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Horbach T, Chi TF, Götz C, Sharma S, Juffer AH, Dimova EY, and Kietzmann T
- Subjects
- Binding Sites, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Gene Expression Regulation, Glycogen Synthase Kinase 3 beta, Half-Life, HeLa Cells, Hep G2 Cells, Humans, Phosphorylation, Transcriptional Activation, Upstream Stimulatory Factors chemistry, Upstream Stimulatory Factors metabolism, Glycogen Synthase Kinase 3 physiology, Upstream Stimulatory Factors physiology
- Abstract
The upstream stimulatory factor 2 (USF2) is a regulator of important cellular processes and is supposed to have also a role during tumor development. However, the knowledge about the mechanisms that control the function of USF2 is limited. The data of the current study show that USF2 function is regulated by phosphorylation and identified GSK3β as an USF2-phosphorylating kinase. The phosphorylation sites within USF2 could be mapped to serine 155 and threonine 230. In silico analyses of the 3-dimensional structure revealed that phosphorylation of USF2 by GSK3β converts it to a more open conformation which may influence transactivity, DNA binding and target gene expression. Indeed, experiments with GSK-3β-deficient cells revealed that USF2 transactivity, DNA binding and target gene expression were reduced upon lack of GSK3β. Further, experiments with USF2 variants mimicking GSK3β phosphorylated USF2 in GSK3β-deficient cells showed that phosphorylation of USF2 by GSK3β did not affect cell proliferation but increased cell migration. Together, this study reports a new mechanism by which USF2 may contribute to cancerogenesis.
- Published
- 2014
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9. Does storage time influence postthaw survival and pregnancy outcome? An analysis of 11,768 cryopreserved human embryos.
- Author
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Riggs R, Mayer J, Dowling-Lacey D, Chi TF, Jones E, and Oehninger S
- Subjects
- Abortion, Spontaneous, Adult, Female, Fertilization in Vitro, Humans, Live Birth, Logistic Models, Odds Ratio, Oocyte Donation, Pregnancy, Pregnancy Rate, Retrospective Studies, Time Factors, Treatment Outcome, Cryopreservation, Embryo Implantation, Embryo Transfer, Embryo, Mammalian, Infertility therapy, Pregnancy Outcome, Reproductive Techniques, Assisted adverse effects
- Abstract
Objective: To evaluate the impact of cryopreservation storage duration on embryo survival, implantation competence, and pregnancy outcome., Design: Retrospective study., Setting: Academic tertiary-referral infertility center., Patient(s): In vitro fertilization patients and recipients of oocyte donation cycles who had cryopreserved embryos and underwent at least one thaw cycle from 1986 to 2007., Intervention(s): None., Main Outcome Measure(s): Postthaw survival proportion and implantation, clinical pregnancy, miscarriage, and live birth rates., Result(s): Length of storage time did not have a significant effect on postthaw survival for IVF or oocyte donation cycles, or for embryos frozen at the pronuclear or cleavage stages. There was no significant impact of the duration of storage on clinical pregnancy, miscarriage, implantation, or live birth rate, whether from IVF or oocyte donation cycles. Logistic regression analysis demonstrated that the length of storage time or developmental stage at freezing were not predictive of embryo survival or pregnancy outcome. Only oocyte age, survival proportion, and number of transferred embryos were positive predictors of pregnancy outcome., Conclusion(s): Cryostorage duration did not adversely affect postthaw survival or pregnancy outcome in IVF or oocyte donation patients., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
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10. Development of a sensitive enzyme-linked immunosorbent assay for the determination of ochratoxin A.
- Author
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Yu FY, Chi TF, Liu BH, and Su CC
- Subjects
- Animals, Antibodies blood, Antibody Specificity, Hemocyanins immunology, Mycotoxins analysis, Ochratoxins immunology, Rabbits, gamma-Globulins immunology, Enzyme-Linked Immunosorbent Assay methods, Ochratoxins analysis
- Abstract
Polyclonal antibodies for ochratoxin A (OTA) were generated from rabbits after the animals had been immunized with either OTA-gamma-globulin or OTA- keyhole limpet hemocyanin (KLH). A competitive direct enzyme-linked immunosorbent assay (cdELISA) and a competitive indirect ELISA (ciELISA) were used for the characterization of the antibodies and for analysis of OTA in various agricultural commodities. The antibody titers in the serum of rabbits immunized with OTA-gamma-globulin were considerably higher than those in rabbits immunized with OTA-KLH. The antibodies from the rabbits immunized with OTA-gamma-globulin were further characterized. In the cdELISA, the concentrations causing 50% inhibition (IC(50)) of binding of OTA-horseradish peroxidase to the antibodies by OTA, ochratoxin B (OTB), and ochratoxin C (OTC) were found to be 0.90, 110, and 0.54 ng/mL, respectively. When 10 to 250 ng/g of standard OTA was spiked to soybean samples and then extracted with 50% aqueous methanol, the recovery rate of OTA was found to be 85.9% in the cdELISA. Analysis of OTA in various agricultural commodities showed that 12 of the 20 examined samples were contaminated with OTA at levels from 16 to 160 ng/g. The efficacy of cdELISA was also confirmed by the high-performance liquid chromatography method.
- Published
- 2005
- Full Text
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11. Development of a sensitive enzyme-linked immunosorbent assay for the determination of domoic Acid in shellfish.
- Author
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Yu FY, Liu BH, Wu TS, Chi TF, and Su MC
- Subjects
- Animals, Antibodies immunology, Bivalvia chemistry, Chromatography, High Pressure Liquid, Hemocyanins immunology, Kainic Acid immunology, Rabbits, Sensitivity and Specificity, Enzyme-Linked Immunosorbent Assay methods, Kainic Acid analogs & derivatives, Kainic Acid analysis, Shellfish analysis
- Abstract
Polyclonal antibodies for domoic acid were generated from rabbits after the animals had been immunized with either domoic acid-keyhole limpet hemocyanin (KLH) or domoic acid-bovine serum albumin (BSA). A competitive direct enzyme-linked immunosorbent assay (cdELISA) and a competitive indirect ELISA (ciELISA) were used for the characterization of the antibodies and for analysis of domoic acid in blue mussels and clams. The antibody titers in the serum of rabbits immunized with domoic acid-KLH were considerably higher than those in rabbits immunized with domoic acid-BSA. The antibodies from the rabbits immunized with domoic acid-KLH were further characterized. In the cdELISA, the concentrations causing 50% inhibition (IC(50)) of binding of domoic acid-horseradish peroxidase to the antibodies by domoic acid and a domoic acid analogue, kainic acid, were found to be 0.75 and 200 ng/mL, respectively. In the presence of blue mussel matrix, the detection limit of domoic acid was <25 ng/g. The overall analytical recovery of domoic acid (25-500 ng/g) added to the blue mussels and then extracted with 50% aqueous methanol in the cdELISA was found to be 81.1%. The efficacy of cdELISA was also confirmed by the high-performance liquid chromatography method. Analysis of domoic acid in shellfish samples showed that 10 of the 15 shellfish examined were contaminated with domoic acid at levels of <50 ng/g.
- Published
- 2004
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12. Characterization of the biologic activities of a recombinant human zona pellucida protein 3 expressed in human ovarian teratocarcinoma (PA-1) cells.
- Author
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Dong KW, Chi TF, Juan YW, Chen CW, Lin Z, Xiang XQ, Mahony M, Gibbons WE, and Oehninger S
- Subjects
- Acrosome Reaction drug effects, Acrosome Reaction physiology, Blotting, Western, Chromatography, Affinity, Chromatography, Ion Exchange, Cloning, Molecular, DNA, Complementary genetics, DNA, Complementary metabolism, Dose-Response Relationship, Drug, Egg Proteins biosynthesis, Egg Proteins genetics, Female, Humans, Male, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins genetics, Ovarian Neoplasms, Ovary metabolism, Pertussis Toxin, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins pharmacology, Reverse Transcriptase Polymerase Chain Reaction, Sperm Capacitation drug effects, Sperm Capacitation physiology, Sperm Motility drug effects, Sperm-Ovum Interactions physiology, Spermatozoa physiology, Transfection, Tumor Cells, Cultured, Virulence Factors, Bordetella pharmacology, Zona Pellucida Glycoproteins, Egg Proteins pharmacology, Membrane Glycoproteins pharmacology, Ovary physiology, Receptors, Cell Surface, Sperm-Ovum Interactions drug effects
- Abstract
Objective: This study was undertaken to clone and express a recombinant human zona pellucida protein 3 and to characterize its biologic activities as a sperm ligand and an inducer of the acrosome reaction., Study Design: Human ovarian teratocarcinoma (PA-1) cells were transfected with an expression vector containing human zona pellucida protein 3 complementary deoxyribonucleic acid with a sequence coding for a 6-histidine tail introduced into its 3' end. Purification of the secreted glycoprotein was performed by sequential affinity (lectin and nickel--nitrilotriacetic acid) and ion-exchange chromatography., Results: Western blot analysis confirmed a molecular weight of approximately 65 kd for the purified product. A cell-free translation system revealed a correctly sized protein backbone of 47 kd. The recombinant human zona pellucida protein 3 demonstrated specific, potent, and dose-dependent competitive inhibition of sperm-zona pellucida binding in vitro under hemizona assay conditions. Recombinant human zona pellucida protein 3 also stimulated the acrosome reaction of live sperm. This effect was fast, dose dependent, and capacitation time dependent. Furthermore, advance incubation with pertussis toxin, an inactivator of heterotrimeric G proteins, blocked recombinant human zona pellucida protein 3--induced acrosomal exocytosis., Conclusion: The recombinant human zona pellucida protein 3 expressed in PA-1 cells manifested the full spectrum of expected biologic activities. It therefore represents a valuable tool for examination of human fertilization and the design of new strategies in diagnosis of male factor infertility and in contraception.
- Published
- 2001
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13. Studies on succinic dehydrogenase. V. The linking between the flavin prosthetic group and the apoenzyme.
- Author
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Chi TF, Wang YL, Tsou CL, Fang YC, and Yu CH
- Subjects
- Animals, Chemical Phenomena, Chemistry, In Vitro Techniques, Sheep, Swine, Flavins, Succinate Dehydrogenase
- Published
- 1965
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