13 results on '"Jing JIN"'
Search Results
2. The E3 Ubiquitin Ligase Neuregulin Receptor Degradation Protein 1 (Nrdp1) Promotes M2 Macrophage Polarization by Ubiquitinating and Activating Transcription Factor CCAAT/Enhancer-binding Protein β (C/EBPβ)
- Author
-
Yizhi Yu, Mingjin Yang, Shuo Ye, Jing Jin, Xuetao Cao, Chunmei Wang, and Hongmei Xu
- Subjects
Transcription, Genetic ,Ubiquitin-Protein Ligases ,Immunology ,Activating transcription factor ,Nitric Oxide Synthase Type II ,Biology ,Polymerase Chain Reaction ,Biochemistry ,Mice ,Ubiquitin ,Animals ,Immunoprecipitation ,Gene Silencing ,Molecular Biology ,Transcription factor ,Interleukin 4 ,DNA Primers ,Arginase ,Base Sequence ,Ccaat-enhancer-binding proteins ,CCAAT-Enhancer-Binding Protein-beta ,Macrophages ,Cell Biology ,M2 Macrophage ,Molecular biology ,Up-Regulation ,Ubiquitin ligase ,Mice, Inbred C57BL ,Interleukin 10 ,NIH 3T3 Cells ,biology.protein ,Cytokines ,Carrier Proteins ,Protein Binding - Abstract
Macrophage activation, including classical (M1) activation and alternative (M2) activation, plays important roles in host immune response and pathogenesis of diseases. Ubiquitination has been shown to be involved in the differentiation of immune cells and in the regulation of immune responses. However, the role of ubiquitination during M1 versus M2 polarization is poorly explored. Here, we showed that arginase 1 (Arg1), a well recognized marker of M2 macrophages, is highly up-regulated in peritoneal macrophages derived from E3 ubiquitin ligase Nrdp1 transgenic (Nrdp1-TG) mice. Furthermore, other M2 feature markers such as MR, Ym1, and Fizz1, as well as Th2 cytokine IL-10, are also up-regulated in Nrdp1-TG macrophages after IL-4 stimulation. Knockdown of Nrdp1 expression effectively inhibits IL-4-induced expression of M2-related genes in macrophages. Moreover, Nrdp1 inhibits LPS-induced production of inducible NOS and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in macrophages. Immunoprecipitation assays show that Nrdp1 interacts with and ubiquitinates transcriptional factor C/EBPβ via Lys-63-linked ubiquitination. Nrdp1 enhances C/EBPβ-triggered transcriptional activation of the Arg1 reporter gene in the presence of IL-4 stimulation. Thus, we demonstrate that Nrdp1-mediated ubiquitination and activation of C/EBPβ contributes to a ubiquitin-dependent nonproteolytic pathway that up-regulates Arg1 expression and promotes M2 macrophage polarization.
- Published
- 2012
3. Correlation of the Tight Junction-like Distribution of Claudin-1 to the Cellular Tropism of Hepatitis C Virus
- Author
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Ronald C. Montelaro, Carolyn B. Coyne, Wei Yang, Nabanita Biswas, Simon C. Watkins, Chao Qiu, Tianyi Wang, and Jing Jin
- Subjects
Hepacivirus ,Tropism ,Biochemistry ,Cell Line ,Tetraspanin 28 ,Tight Junctions ,HeLa ,Mice ,Antigens, CD ,Claudin-1 ,Animals ,Humans ,Claudin ,Molecular Biology ,Glycoproteins ,Tight junction ,biology ,HEK 293 cells ,Virion ,Membrane Proteins ,Cell Biology ,Virus Internalization ,biology.organism_classification ,Cell biology ,Membrane Transport, Structure, Function, and Biogenesis ,Cell culture ,Ectopic expression ,Protein Binding ,CD81 - Abstract
Claudin-1 (CLDN1), a tight junction (TJ) protein, has recently been identified as an entry co-receptor for hepatitis C virus (HCV). Ectopic expression of CLDN1 rendered several non-hepatic cell lines permissive to HCV infection. However, little is known about the mechanism by which CLDN1 mediates HCV entry. It is believed that an additional entry receptor(s) is required because ectopic expression of CLDN1 in both HeLa and NIH3T3 cells failed to confer susceptibility to viral infection. Here we found that CLDN1 was co-immunoprecipitated with both HCV envelope proteins when expressed in 293T cells. Results from biomolecular fluorescence complementation assay showed that overexpressed CLDN1 also formed complexes with CD81 and low density lipoprotein receptor. Subsequent imaging analysis revealed that CLDN1 was highly enriched at sites of cell-cell contact in permissive cell lines, co-localizing with the TJ marker, ZO-1. However, in both HeLa and NIH3T3 cells the ectopically expressed CLDN1 appeared to reside predominantly in intracellular vesicles. The CLDN1-CD81 complex formed in HeLa cells was also exclusively distributed intracellularly, co-localizing with EEA1, an early endosomal marker. Correspondingly, transepithelial electric resistance, obtained from the naturally susceptible human liver cell line, Huh7, was much higher than that of the HeLa-CLDN1 cell line, suggesting that Huh7 is likely to form functional tight junctions. Finally, the disruption of TJ-enriched CLDN1 by tumor necrosis factor-α treatment markedly reduced the susceptibility of Huh7.5.1 cells to HCV infection. Our results suggest that the specific localization pattern of CLDN1 may be crucial in the regulation of HCV cellular tropism.
- Published
- 2008
4. Inhibition of Nucleoside Transport by p38 MAPK Inhibitors
- Author
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Lee M. Graves, Jing Jin Gu, Min Huang, Yanhong Wang, Beverly S. Mitchell, and Matthew A. Collins
- Subjects
Erythrocytes ,p38 mitogen-activated protein kinases ,AraC Transcription Factor ,Biology ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,chemistry.chemical_compound ,Bacterial Proteins ,In vivo ,Humans ,Enzyme Inhibitors ,Uridine ,Molecular Biology ,Chromatography, High Pressure Liquid ,Dose-Response Relationship, Drug ,Kinase ,Cell Membrane ,Biological Transport ,Nucleosides ,Equilibrative nucleoside transporter ,Transporter ,Cell Biology ,Molecular biology ,Repressor Proteins ,Models, Chemical ,chemistry ,lipids (amino acids, peptides, and proteins) ,Mitogen-Activated Protein Kinases ,K562 Cells ,Nucleoside ,Protein Binding ,Transcription Factors ,K562 cells - Abstract
While investigating the ability of p38 MAPK to regulate cytarabine (Ara C)-dependent differentiation of erythroleukemia K562 cells, we observed effects that indicated that the imidazoline class of p38 MAPK inhibitors prevented nucleoside transport. Incubation of K562 cells with SB203580, SB203580-iodo, or SB202474, an analogue of SB203580 that does not inhibit p38 MAPK activity, inhibited the uptake of [3H]Ara C or [3H]uridine and the differentiation of K562 cells. Consistent with the effects of these compounds on the nitrobenzylthioinosine (NBMPR)-sensitive equilibrative nucleoside transporter (ENT1), incubation with SB203580 or SB203580-iodo eliminated the binding of [3H]NBMPR to K562 cells or membranes isolated from human erythrocytes. Furthermore, using a uridine-dependent cell type (G9c), we observed that SB203580 or SB203580-iodo efficiently inhibited the salvage synthesis of pyrimidine nucleotides in vivo. Thus these studies demonstrate that the NBMPR-sensitive equilibrative nucleoside transporters are novel and unexpected targets for the p38 MAPK inhibitors at concentrations typically used to inhibit protein kinases.
- Published
- 2002
5. Opposite Translational Control of GLUT1 and GLUT4 Glucose Transporter mRNAs in Response to Insulin
- Author
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Hadi Al-Hasani, Celia Taha, Nahum Sonenberg, Zhi Liu, Amira Klip, and Jing Jin
- Subjects
endocrine system ,biology ,Akt/PKB signaling pathway ,Insulin ,medicine.medical_treatment ,nutritional and metabolic diseases ,Translation (biology) ,Cell Biology ,mTORC1 ,Biochemistry ,Molecular biology ,carbohydrates (lipids) ,Eukaryotic initiation factor ,Polysome ,biology.protein ,medicine ,Molecular Biology ,Protein kinase B ,hormones, hormone substitutes, and hormone antagonists ,GLUT4 - Abstract
Prolonged exposure of 3T3-L1 adipocytes to insulin increases GLUT1 protein content while diminishing GLUT4. These changes arise in part from changes in mRNA transcription. Here we examined whether there are also specific effects of insulin on GLUT1 and GLUT4 mRNA translation. Insulin enhanced association of GLUT1 mRNA with polyribosomes and decreased association with monosomes, suggesting increased translation. Conversely, insulin arrested the majority of GLUT4 transcripts in monosomes. Insulin inactivates the translational suppressor eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) through the mammalian target of rapamycin (mTOR). Hence, we examined the effect of rapamycin on GLUT1 mRNA translation and protein expression. Rapamycin abrogated the insulin-mediated increase in GLUT1 protein synthesis through partial inhibition of GLUT1 mRNA translation and partial inhibition of the rise in GLUT1 mRNA. 4E-BP1 inhibited GLUT1 mRNA translationin vitro. Because phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB), in concert with mTOR, inactivate 4E-BP1, we explored their role in GLUT1 protein expression. Cotransfection of cytomegalovirus promoter-driven, hemagglutinin epitope-taggedGLUT1 with dominant inhibitory mutants of PI3K or PKB inhibited the insulin-elicited increase in hemagglutinin-tagged GLUT1 protein. These results unravel the opposite effects of insulin on GLUT1 and GLUT4 mRNA translation. Increased GLUT1 mRNA translation appears to occur via the PI3K/PKB/mTOR/4E-BP1 cascade.
- Published
- 1999
6. Regulation of the Human Inosine Monophosphate Dehydrogenase Type I Gene
- Author
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Jozef Spychala, Beverly S. Mitchell, and Jing Jin Gu
- Subjects
Gene isoform ,Messenger RNA ,IMP dehydrogenase ,Transcription (biology) ,Gene expression ,Transcriptional regulation ,Promoter ,Cell Biology ,Biology ,Molecular Biology ,Biochemistry ,Molecular biology ,Gene - Abstract
Catalysis of guanine nucleotide formation from IMP in the de novo purine synthetic pathway is carried out by two isoforms of the enzyme inosine monophosphate dehydrogenase (IMPDH) that are catalytically indistinguishable but are encoded by separate genes. In order to assess the potential for cell type-specific expression of IMPDH activity, we have characterized the IMPDH type I gene and identified three major RNA transcripts that are differentially expressed from three different promoters. A 4.0-kilobase pair (kb) mRNA containing 1.3 kb of 5′-untranslated region is expressed in activated peripheral blood lymphocytes and to a far lesser extent in cultured tumor cell lines. The P1 promoter that regulates the transcription of this mRNA has a high degree of sequence identity to an Alu repetitive sequence. A transcript of 2.7 kb is found in a subset of the tumor cell lines examined, whereas a 2.5-kb mRNA species is universally expressed and is the prevalent mRNA in most cell lines and tissues. The relative strengths of the three promoter regions and the effects of variable extents of 5′-flanking sequence on the P3 promoter differ in Jurkat T, as compared with Raji B lymphoid cell lines, demonstrating a complex cell type-specific transcriptional regulation of IMPDH type I gene expression.
- Published
- 1997
7. Inhibition of Nucleoside Transport by p38 MAPK Inhibitors
- Author
-
Huang, Min, primary, Wang, Yanhong, additional, Collins, Matthew, additional, Gu, Jing Jin, additional, Mitchell, Beverly S., additional, and Graves, Lee M., additional
- Published
- 2002
- Full Text
- View/download PDF
8. Regulation of the Human Inosine Monophosphate Dehydrogenase Type I Gene
- Author
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Gu, Jing Jin, primary, Spychala, Jozef, additional, and Mitchell, Beverly S., additional
- Published
- 1997
- Full Text
- View/download PDF
9. trans-(-)-ϵ-Viniferin Increases Mitochondrial Sirtuin 3 (SIRT3), Activates AMP-activated Protein Kinase (AMPK), and Protects Cells in Models of Huntington Disease.
- Author
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Jinrong Fu, Jing Jin, Cichewicz, Robert H., Hageman, Serena A., Ellis, Trevor K., Lan Xiang, Qi Peng, Mali Jiang, Arbez, Nicolas, Hotaling, Katelyn, Ross, Christopher A., and Wenzhen Duan
- Subjects
- *
SIRTUINS , *PROTEIN kinases , *HUNTINGTON disease , *POLYGLUTAMINE , *HUNTINGTIN protein , *MITOCHONDRIA - Abstract
Huntington disease (HD) is an inherited neurodegenerative disorder caused by an abnormal polyglutamine expansion in the protein Huntingtin (Htt). Currently, no cure is available for HD. The mechanisms by which mutant Htt causes neuronal dysfunction and degeneration remain to be fully elucidated. Nevertheless, mitochondrial dysfunction has been suggested as a key event mediating mutant Htt-induced neurotoxicity because neurons are energy-demanding and particularly susceptible to energy deficits and oxidative stress. SIRT3, a member of sirtuin family, is localized to mitochondria and has been implicated in energy metabolism. Notably, we found that cells expressing mutant Htt displayed reduced SIRT3 levels. trans-(-)-ϵ -Viniferin (viniferin), a natural product among our 22 collected naturally occurring and semisynthetic stilbenic compounds, significantly attenuated mutant Htt-induced depletion of SIRT3 and protected cells from mutant Htt. We demonstrate that viniferin decreases levels of reactive oxygen species and prevents loss of mitochondrial membrane potential in cells expressing mutant Htt. Expression of mutant Htt results in decreased deacetylase activity of SIRT3 and further leads to reduction in cellular NAD+ levels and mitochondrial biogenesis in cells. Viniferin activates AMP-activated kinase and enhances mitochondrial biogenesis. Knockdown of SIRT3 significantly inhibited viniferin- mediated AMP-activated kinase activation and diminished the neuroprotective effects of viniferin, suggesting that SIRT3 mediates the neuroprotection of viniferin. In conclusion, we establish a novel role for mitochondrial SIRT3 in HD pathogenesis and discovered a natural product that has potent neuroprotection in HD models. Our results suggest that increasing mitochondrial SIRT3 might be considered as a new therapeutic approach to counteract HD, as well as other neurodegenerative diseases with similar mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
10. The E3 Ubiquitin Ligase Neuregulin Receptor Degradation Protein 1 (Nrdp1) Promotes M2 Macrophage Polarization by Ubiquitinating and Activating Transcription Factor CCAAT/Enhancer-binding Protein β (C/EBPβ).
- Author
-
Shuo Ye, Hongmei Xu, Jing Jin, Mingjin Yang, Chunmei Wang, Yizhi Yu, and Xuetao Cao
- Subjects
- *
UBIQUITIN ligases , *POLARIZATION (Nuclear physics) , *TRANSCRIPTION factors , *CELLULAR immunity , *CARRIER proteins , *CYTOKINES - Abstract
Macrophage activation, including classical (M1) activation and alternative (M2) activation, plays important roles in host immune response and pathogenesis of diseases. Ubiquitination has been shown to be involved in the differentiation of immune cells and in the regulation of immune responses. However, the role of ubiquitination during M1 versus M2 polarization is poorly explored. Here, we showed that arginase 1 (Arg1), a well recognized marker of M2 macrophages, is highly up-regulated in peritoneal macrophages derived from E3 ubiquitin ligase Nrdp1 transgenic (Nrdp1-TG) mice. Furthermore, other M2 feature markers such as MR, Ym1, and Fizz1, as well as Th2 cytokine IL-10, are also up-regulated in Nrdp1-TG macrophages after IL-4 stimulation. Knockdown of Nrdp1 expression effectively inhibits IL-4-induced expression of M2-related genes in macrophages. Moreover, Nrdp1 inhibits LPS-induced production of inducible NOS and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in macrophages. Immunoprecipitation assays show that Nrdp1 interacts with and ubiquitinates transcriptional factor C/EBPβ via Lys-63-linked ubiquitination. Nrdp1 enhances C/EBPβ-triggered transcriptional activation of the Arg1 reporter gene in the presence of IL-4 stimulation. Thus, we demonstrate that Nrdp1-mediated ubiquitination and activation of C/EBPβ contributes to a ubiquitin-dependent nonproteolytic pathway that up-regulates Arg1 expression and promotes M2 macrophage polarization. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
11. Functions of Early (AP-2) and Late (AIP1/ALIX) Endocytic Proteins in Equine Infectious Anemia Virus Budding.
- Author
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Chaoping Chen, Vincent, Olivier, Jing Jin, Weisz, Ora A., and Montelaro, Ronald C.
- Subjects
- *
PROLINE , *HIV , *RETROVIRUSES , *PROTEINS , *ANEMIA , *SMALL interfering RNA , *GENE expression , *GENE silencing - Abstract
The proline-rich L domains of human immunodeficiency virus 1 (HIV-1) and other retroviruses interact with late endocytic proteins during virion assembly and budding. In contrast, the YPDL L domain of equine infectious anemia virus (EIAV) is apparently unique in its reported ability to interact both with the μ2 subunit of the AP-2 adaptor protein complex and with ALG-2-interacting protein 1 (AIP1/Alix) protein factors involved in early and late endosome formation, respectively. To define further the mechanisms by which EIAV adapts vesicle trafficking machinery to facilitate virion production, we have examined the specificity of EIAV p9 binding to endocytic factors and the effects on virion production of alterations in early and late endocytic protein expression. The results of these studies demonstrated that (i) an ∼300-residue region of AIP1/Alix-(409–715) was sufficient for binding to the EIAV YPDL motif; (ii) overexpression of AIP1/Alix or AP-2 μ2 subunit specifically inhibited YPDL-mediated EIAV budding; (iii) virion budding from a replication-competent EIAV variant with its L domain replaced by the HIV PTAP sequence was inhibited by wild type or mutant μ2 to a level similar to that observed when a dominant-negative mutant of Tsg101 was expressed; and (iv) overexpression or siRNA silencing of AIP1/Alix and AP-2 revealed additive suppression of YPDL-mediated EIAV budding. Taken together, these results indicated that both early and late endocytic proteins facilitate EIAV production mediated by either YPDL or PTAPL domains, suggesting a comprehensive involvement of endocytic factors in retroviral assembly and budding that can be accessed by distinct L domain specificities. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
12. Tyrosine Kinase Btk Is Required for NK Cell Activation.
- Author
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Yan Bao, Jian Zheng, Chaofeng Han, Jing Jin, Huanxing Han, Yinping Liu, Yu-Lung Lau, Wenwei Tu, and Xuetao Cao
- Subjects
- *
PROTEIN-tyrosine kinases , *KILLER cells , *B cells , *MACROPHAGES , *IMMUNE response , *LIVER diseases , *X-linked inhibitor of apoptosis protein , *AGAMMAGLOBULINEMIA - Abstract
Bruton tyrosine kinase (Btk) is not only critical for B cell development and differentiation but is also involved in the regulation of Toll-like receptor-triggered innate response of macrophages. However, whether Btk is involved in the regulation of natural killer (NK) cell innate function remains unknown. Here, we show that Btk expression is up-regulated during maturation and activation of mouse NK cells. Murine Btk-/- NKcells have decreased innate immune responses to the TLR3 ligand, with reduced expressions of IFN-γ, perforin, and granzyme-B and decreased cytotoxic activity. Furthermore, Btk is found to promote TLR3-triggered NK cell activation mainly by activating the NF-κB pathway. Poly(I:C)-induced NK cellmediated acute hepatitis was observed to be attenuated in -/- mice or the mice with in vivo administration of the Btk inhibitor. Correspondingly, liver damage was aggravated in -/- mice after the adoptive transfer of Btk-/- NK cells, further indicating that Btk-mediated NK cell activation contributes to TLR3-triggered acute liver injury. Importantly, reduced TLR3-triggered activation of human NK cells was observed in Btk-deficient patients with X-linked agammaglobulinemia, as evidenced by the reduced IFN-γ, CD69, and CD107a expression and cytotoxic activity. These results indicate that Btk is required for activation of NK cells, thus providing insight into the physiological significance of Btk in the regulation of immune cell functions and innate inflammatory response. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
13. Correlation of the Tight Junction-like Distribution of Claudin-1 to the Cellular Tropism of Hepatitis C Virus.
- Author
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Wei Yang, Chao Qiu, Biswas, Nabanita, Jing Jin, Watkinst, Simon C., Montelaro, Ronald C., Coyne, Carolyn B., and Tianyi Wang
- Subjects
- *
PROTEINS , *LIVER cells , *VIRUS diseases , *LOW density lipoproteins , *CELL lines - Abstract
Claudin-1 (CLDN1), a tight junction (TJ) protein, has recently been identified as an entry co-receptor for hepatitis C virus (HCV), Ectopic expression of CLDN1 rendered several non-hepatic cell lines permissive to HCV infection. However, little is known about the mechanism by which CLDN1 mediates HCV entry. It is believed that an additional entry receptor(s) is required because ectopic expression of CLDN1 in both HeLa and NIH3T3 cells failed to confer susceptibility to viral infection. Here we found that CLDN1 was co-immunoprecipitated with both HCV envelope proteins when expressed in 293T cells. Results from biomolecular fluorescence complementation assay showed that overexpressed CLDN1 also formed complexes with CD81 and low density lipoprotein receptor. Subsequent imaging analysis revealed that CLDN1 was highly enriched at sites of cell-cell contact in permissive cell lines, co-localizing with the TJ marker, ZO-1. However, in both HeLa and NIH3T3 cells the ectopically expressed CLDN1 appeared to reside predominantly in intracellular vesicles. The CLDN1-CD81 complex formed in HeLa cells was also exclusively distributed intracellularly, co-localizing with EEA1, an early endosomal marker. Correspondingly, transepithelial electric resistance, obtained from the naturally susceptible human liver cell line, Huh7, was much higher than that of the HeLa-CLDN1 cell line, suggesting that Huh7 is likely to form functional tight junctions. Finally, the disruption of TJ-enriched CLDN1 by tumor necrosis factor-α treatment markedly reduced the susceptibility of Huh7.5.1 cells to HCV infection. Our results suggest that the specific localization pattern of CLDN1 may be crucial in the regulation of HCV cellular tropism. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
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