scholarly journals Cleavage of DAP5 by coxsackievirus B3 protease 2A causes its nuclear translocation and inhibition of IRES‐containing gene transcription (836.5)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Paul Hanson ◽  
Ye Qiu ◽  
Xin Ye ◽  
Huifang Mary Zhang ◽  
Maged Hemida ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Nuclear Translocation ◽  
Coxsackievirus B3 ◽  
Protease 2A

scholarly journals p85α Acts as a Novel Signal Transducer for Mediation of Cellular Apoptotic Response to UV Radiation

2007 ◽  
Vol 27 (7) ◽  
pp. 2713-2731 ◽  
Author(s):  
Lun Song ◽  
Jingxia Li ◽  
Jianping Ye ◽  
Gang Yu ◽  
Jin Ding ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Uv Radiation ◽  
Gene Transcription ◽  
Cell Apoptosis ◽  
Cellular Response ◽  
Nuclear Translocation ◽  
Site Directed Mutagenesis ◽  
Regulatory Subunit ◽  
Special Effect ◽  
Tnf Α

ABSTRACT Apoptosis is an important cellular response to UV radiation (UVR), but the corresponding mechanisms remain largely unknown. Here we report that the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI-3K) exerted a proapoptotic role in response to UVR through the induction of tumor necrosis factor alpha (TNF-α) gene expression. This special effect of p85α was unrelated to the PI-3K-dependent signaling pathway. Further evidence demonstrated that the inducible transcription factor NFAT3 was the major downstream target of p85α for the mediation of UVR-induced apoptosis and TNF-α gene transcription. p85α regulated UVR-induced NFAT3 activation by modulation of its nuclear translocation and DNA binding and the relevant transcriptional activities. Gel shift assays and site-directed mutagenesis allowed the identification of two regions in the TNF-α gene promoter that served as the NFAT3 recognition sequences. Chromatin immunoprecipitation assays further confirmed that the recruitment of NFAT3 to the endogenous TNF-α promoter was regulated by p85α upon UVR exposure. Finally, the knockdown of the NFAT3 level by its specific small interfering RNA decreased UVR-induced TNF-α gene transcription and cell apoptosis. The knockdown of endogenous p85α blocked NFAT activity and TNF-α gene transcription, as well as cell apoptosis. Thus, we demonstrated p85α-associated but PI-3K-independent cell death in response to UVR and identified a novel p85α/NFAT3/TNF-α signaling pathway for the mediation of cellular apoptotic responses under certain stress conditions such as UVR.

Induction of HOXA3 by PRRSV inhibits IFN-I response through negatively regulation of HO-1 transcription

2021 ◽  
Author(s):  
Yingtong Feng ◽  
Xuyang Guo ◽  
Hong Tian ◽  
Yuan He ◽  
Yang Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Transcription ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Host Cells ◽  
Type I Interferons ◽  
Economic Losses ◽  
Heme Oxygenase 1 ◽  
Type I

Type I interferons (IFN-I) play a key role in the host defense against virus infection, but porcine reproductive and respiratory syndrome virus (PRRSV) infection does not effectively activate IFN-I response, and the underlying molecular mechanisms are poorly characterized. In this study, a novel transcription factor of the heme oxygenase-1 (HO-1) gene, homeobox A3 (HOXA3), was screened and identified. Here, we found that HOXA3 was significantly increased during PRRSV infection. We demonstrated that HOXA3 promotes PRRSV replication by negatively regulating the HO-1 gene transcription, which is achieved by regulating type I interferons (IFN-I) production. A detailed analysis showed that PRRSV exploits HOXA3 to suppress beta interferon (IFN-β) and IFN-stimulated gene (ISG) expression in host cells. We also provide direct evidence that the activation of IFN-I by HO-1 depends on its interaction with IRF3. Then we further proved that deficiency of HOXA3 promoted the HO-1-IRF3 interaction, and subsequently enhanced IRF3 phosphorylation and nuclear translocation in PRRSV-infected cells. These data suggest that PRRSV uses HOXA3 to negatively regulate the transcription of the HO-1 gene to suppress the IFN-I response for immune evasion. IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, leads the pork industry worldwide to significant economic losses. HOXA3 is generally considered to be an important molecule in the process of body development and cell differentiation. Here, we found a novel transcription factor of the HO-1 gene, HOXA3, can negatively regulate the transcription of the HO-1 gene and play an important role in the suppression of IFN-I response by PRRSV. PRRSV induces the upregulation of HOXA3, which can negatively regulate HO-1 gene transcription, thereby weakening the interaction between HO-1 and IRF3 for inhibiting the type I IFN response. This study extends the function of HOXA3 to the virus field for the first time and provides new insights into PRRSV immune evasion mechanism.

scholarly journals USP11 augments TGFβ signalling by deubiquitylating ALK5

Open Biology ◽  
2012 ◽  
Vol 2 (6) ◽  
pp. 120063 ◽  
Author(s):  
Mazin A. Al-Salihi ◽  
Lina Herhaus ◽  
Thomas Macartney ◽  
Gopal P. Sapkota
Keyword(s):  
Gene Transcription ◽  
Epithelial To Mesenchymal Transition ◽  
Nuclear Translocation ◽  
Type I ◽  
Negative Effects ◽  
Transcriptional Responses ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Tgfβ Signalling ◽  
Tgfβ Pathway

Summary The TGFβ receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFβ signals, negatively regulates the TGFβ pathway by recruiting E3 ubiquitin ligases and targeting TGFβ receptors for ubiquitin-mediated degradation. In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFβ signalling and can override the negative effects of SMAD7. USP11 interacts with and deubiquitylates the type I TGFβ receptor (ALK5), resulting in enhanced TGFβ-induced gene transcription. The deubiquitylase activity of USP11 is required to enhance TGFβ-induced gene transcription. RNAi -mediated depletion of USP11 results in inhibition of TGFβ-induced SMAD2/3 phosphorylation and TGFβ-mediated transcriptional responses. Central to TGFβ pathway signalling in early embryogenesis and carcinogenesis is TGFβ-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFβ-induced epithelial to mesenchymal transition.

Stimulation by lithium of the interaction between the transcription factor CREB and its co-activator TORC

2009 ◽  
Vol 29 (2) ◽  
pp. 77-87 ◽  
Author(s):  
Annette Heinrich ◽  
Ulrike Böer ◽  
Mladen Tzvetkov ◽  
Elke Oetjen ◽  
Willhart Knepel
Keyword(s):  
Transcription Factor ◽  
Gene Transcription ◽  
Glutathione Transferase ◽  
Nuclear Translocation ◽  
Camp Response Element Binding ◽  
Lithium Salts ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
A Cell ◽  
Novel Target

Lithium salts are clinically important drugs used to treat bipolar mood disorder. The mechanisms accounting for the clinical efficacy are not completely understood. Chronic treatment with lithium is required to establish mood stabilization, suggesting the involvement of neuronal plasticity processes. CREB (cAMP-response-element-binding protein) is a transcription factor known to mediate neuronal adaptation. Recently, the CREB-co-activator TORC (transducer of regulated CREB) has been identified as a novel target of lithium and shown to confer an enhancement of cAMP-induced CREB-directed gene transcription by lithium. TORC is sequestered in the cytoplasm and its nuclear translocation controls CREB activity. In the present study, the effect of lithium on TORC function was investigated. Lithium affected neither the nuclear translocation of TORC nor TORC1 transcriptional activity, but increased the promoter occupancy by TORC1 as revealed by chromatin immunoprecipitation assay. In a mammalian two-hybrid assay, as well as in a cell-free GST (glutathione transferase) pull-down assay, lithium enhanced the CREB–TORC1 interaction. Magnesium ions strongly inhibited the interaction between GST–CREB and TORC1 and this effect was reversed by lithium. Thus our results suggest that, once TORC has entered the nucleus, lithium as a cation stimulates directly the binding of TORC to CREB, leading to an increase in cAMP-induced CREB target-gene transcription. This novel mechanism of lithium action is likely to contribute to the clinical mood-stabilizing effect of lithium salts.

scholarly journals Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription

1999 ◽  
Vol 19 (2) ◽  
pp. 959-966 ◽  
Author(s):  
Rongtuan Lin ◽  
Christophe Heylbroeck ◽  
Pierre Genin ◽  
Paula M. Pitha ◽  
John Hiscott
Keyword(s):  
Virus Infection ◽  
Gene Transcription ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Dominant Negative ◽  
Transactivation Potential ◽  
Infected Cells ◽  
Systemic Cytokine Production ◽  
Rantes Promoter

ABSTRACT Localized and systemic cytokine production in virus-infected cells play an important role in the outcome of viral infection and pathogenicity. Activation of the interferon regulatory factors (IRF) in turn is a critical mediator of cytokine gene transcription. Recent studies have focused on the 55-kDa IRF-3 gene product as a direct transcriptional regulator of type 1 interferon (IFN-α and IFN-β) activation in response to virus infection. Virus infection induces phosphorylation of IRF-3 on specific C-terminal serine residues and permits cytoplasmic-to-nuclear translocation of IRF-3, activation of DNA binding and transactivation potential, and association with the CBP/p300 coactivator. We previously generated constitutively active [IRF-3(5D)] and dominant-negative forms of IRF-3 that control IFN-β and IFN-α gene expression. In an effort to characterize the range of immunoregulatory genes controlled by IRF-3, we now demonstrate that endogenous human RANTES gene transcription is directly induced in tetracycline-inducible IRF-3(5D)-expressing cells or paramyxovirus-infected cells. We also show that a dominant-negative IRF-3 mutant inhibits virus-induced expression of the RANTES promoter. Specific mutagenesis of overlapping ISRE-like sites located between nucleotides −123 and −96 in the RANTES promoter reduces virus-induced and IRF-3-dependent activation. These studies broaden the range of IRF-3 immunoregulatory target genes to include at least one member of the chemokine superfamily.

scholarly journals Pdx-1 Is Not Sufficient for Repression of Proglucagon Gene Transcription in Islet or Enteroendocrine Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 441-449 ◽  
Author(s):  
Grace Flock ◽  
Xiemin Cao ◽  
Daniel J. Drucker
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Nuclear Translocation ◽  
Immunohistochemical Analysis ◽  
Enteroendocrine Cells ◽  
Cell Phenotype ◽  
Protein Overexpression ◽  
Adenoviral Transduction ◽  
Glucagon Like Peptide 1 ◽  
The Relationship

Pdx-1 plays a key role in the development of the pancreas and the control of islet gene transcription and has also been proposed as a dominant regulator of the α- vs. β-cell phenotype via extinction of proglucagon expression. To ascertain the relationship between Pdx-1 and proglucagon gene expression, we examined the effect of enhanced pdx-1 expression on proglucagon gene expression in murine islet αTC-1 and GLUTag enteroendocrine cells. Although adenoviral transduction increased the levels of pdx-1 mRNA transcripts and nuclear Pdx-1 protein, overexpression of pdx-1 did not repress endogenous proglucagon gene expression in αTC-1 or GLUTag cells or murine islets. Immunohistochemical analysis of cells transduced with Ad-pdx-1 demonstrated multiple individual islet or enteroendocrine cells exhibiting both nuclear Pdx-1 and cytoplasmic glucagon-like peptide-1 immunopositivity. The failure of pdx-1 to inhibit endogenous proglucagon gene expression was not attributable to defects in Pdx-1 nuclear translocation or DNA binding as demonstrated using Western blotting and EMSA analyses. Furthermore, Ad-pdx-1 transduction did not repress proglucagon promoter activity in αTC-1 or GLUTag cells. Taken together, these findings demonstrate that pdx-1 alone is not sufficient for specification of the hormonal phenotype or extinction of proglucagon gene expression in islet or enteroendocrine cells.

scholarly journals CNBP controls c-Rel dependent IL-12β gene transcription and Th1 immunity

2018 ◽  
Author(s):  
Yongzhi Chen ◽  
Shruti Sharma ◽  
Patricia A. Assis ◽  
Zhaozhao Jiang ◽  
Andrew J. Olive ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Nuclear Translocation ◽  
Binding Activity ◽  
Nucleic Acid Binding ◽  
Th1 Cell ◽  
Inflammatory Gene Expression ◽  
Dna Binding Activity ◽  
Parasite Replication ◽  
Acute Toxoplasmosis ◽  
Selective Impairment

SummaryAn inducible program of inflammatory gene expression is a hallmark of antimicrobial defenses. Herein, we identified Cellular nucleic acid binding protein (Cnbp) as a specific regulator of interleukin-12β gene transcription and Th1 immunity. Cnbp resides in the cytosol of macrophages and translocates to the nucleus in response to a broad range of microbial ligands. Cnbp-deficient macrophages had a selective impairment in their ability to induce IL12β gene transcription. Cnbp interacted with c-Rel, an NFκB/Rel family member that controls IL12β gene transcription. c-Rel nuclear translocation and DNA binding activity were dependent on Cnbp. Furthermore, Cnbp itself bound the IL12β promoter. Lastly, Cnbp-deficient mice were more susceptible to acute toxoplasmosis associated with reduced production of IL12β, as well as a reduced Th1 cell IFNγ response essential to control parasite replication. Collectively, these findings identify Cnbp as a key regulator of c-Rel dependent IL12β gene transcription and Th1 immunity.

scholarly journals Actomyosin contractility modulates Wnt signaling through adherens junction stability

2017 ◽  
Author(s):  
Eric T. Hall ◽  
Elizabeth Hoesing ◽  
Endre Sinkovics ◽  
Esther M. Verheyen
Keyword(s):  
Wnt Signaling ◽  
Gene Transcription ◽  
Target Gene ◽  
Nuclear Translocation ◽  
Adherens Junctions ◽  
Wnt Signaling Pathway ◽  
Epithelial Tissue ◽  
Actomyosin Contractility ◽  
Target Gene Transcription ◽  
E Cadherin

AbstractMechanical forces can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis, but a molecular mechanism involving both in a developing epithelium and its homeostasis is lacking. We identified that increased non-muscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila. Genetic interactions studies identified this effect was due to myosin-induced accumulation of cortical F-actin resulting in clustering and accumulation of E-cadherin to the adherens junctions. E-cadherin titrates any available β-catenin, the Wnt pathway transcriptional co-activator, to the adherens junctions in order to maintain cell-cell adhesion under contraction. We show that decreased levels of cytoplasmic β-catenin result in insufficient nuclear translocation for full Wnt target gene transcription. Our work elucidates a mechanism in which the dynamic activation of actomyosin contractility refines patterning of Wnt transcription during development and maintenance of epithelial tissue in organisms.

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