scholarly journals Role of Gα12 and Gα13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

2007 ◽  
Vol 27 (17) ◽  
pp. 6195-6208 ◽  
Author(s):  
Min Kyung Cho ◽  
Won Dong Kim ◽  
Sung Hwan Ki ◽  
Jong-Ik Hwang ◽  
Sangdun Choi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Target Gene ◽  
Target Genes ◽  
Gene Knockout ◽  
Serine Phosphorylation ◽  
Related Factor ◽  
Dependent Signal ◽  
Extracellular Stimuli ◽  
Target Gene Induction

ABSTRACT Gα12 and Gα13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by Gα12 and Gα13. A deficiency of Gα12, but not of Gα13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, Gα12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by Gα12 gene knockout. Gα12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did Gα13 deficiency. The absence of Gα12, but not of Gα13, increased protein kinase C δ (PKC δ) activation and the PKC δ-mediated serine phosphorylation of Nrf2. Gα13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by Gα12 deficiency, suggesting that relief from Gα12 repression leads to the Gα13-mediated activation of Nrf2. Constitutive activation of Gα13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC δ activation, corroborating positive regulation by Gα13. In summary, Gα12 and Gα13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas Gα13 regulates Rho-PKC δ-mediated Nrf2 phosphorylation, which is negatively balanced by Gα12.

scholarly journals CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 ◽  
Vol 19 (1) ◽  
pp. 495-504 ◽  
Author(s):  
John Sok ◽  
Xiao-Zhong Wang ◽  
Nikoleta Batchvarova ◽  
Masahiko Kuroda ◽  
Heather Harding ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Target Gene ◽  
Target Genes ◽  
Direct Evidence ◽  
Nuclear Protein ◽  
Intracellular Form ◽  
Carbonic Anhydrase Vi ◽  
Responsive Element

ABSTRACT CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducibleCA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VIexpression in c/ebpβ−/− cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

Study on the Function of miRNA-155 Target Using Bioinformatics Methods

2013 ◽  
Vol 709 ◽  
pp. 858-861
Author(s):  
De Ming Han ◽  
Zi Jun Shen ◽  
Li Hui Zhao
Keyword(s):  
Protein Expression ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Gene Prediction ◽  
Diagnosis And Treatment ◽  
Transcriptional Level ◽  
Mirna Target Gene ◽  
Non Coding Rnas

MicroRNAs are small non-coding RNAs that act at the post-transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. We searched information about miR-155 in miRBase. Target genes of miR-155 are predicted by four miRNA target gene prediction softwares. The result shows that miR-155 was involved in proliferation, differentiation and apoptosis. These results can contribute to further study on the role of microRNA in diagnosis and treatment of cancer.

scholarly journals MicroRNA-381 Negatively Regulates TLR4 Signaling in A549 Cells in Response to LPS Stimulation

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhihao Xu ◽  
Dapeng Dong ◽  
Xiaofei Chen ◽  
Huaqiong Huang ◽  
Shenglan Wen
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Respiratory Infections ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Elisa Kit ◽  
Cox 2

It is widely reported that miR-381 is dysregulated in various tumors. However, the specific role of miR-381 in respiratory infections has not been reported. To probe this role, A549 cells were pretreated with 1 μg/mL LPS for 24 h. The level of miR-381 was detected using RT-qPCR. The expression of proinflammatory cytokines was determined using an ELISA kit and western blotting. Bioinformatics analysis was used to predict the target genes of miR-381, and a luciferase reporter assay was used to validate the expression of the target genes. miR-381 expression was increased in A549 cells treated with LPS, which is a ligand of TLRs. Further study revealed that the overexpression of miR-381 increased the activity of NF-κB signaling, thereby increasing the expression of IL-6, TNFα, and COX-2. Further study revealed that IκBα was a target gene of miR-381. The upregulation of miR-381 under LPS stimulation contributes to respiratory infections mainly by targeting IκBα.

scholarly journals Role of Active Efflux in Association with Target Gene Mutations in Fluoroquinolone Resistance in Clinical Isolates of Vibrio cholerae

2002 ◽  
Vol 46 (8) ◽  
pp. 2676-2678 ◽  
Author(s):  
Somesh Baranwal ◽  
Keya Dey ◽  
T. Ramamurthy ◽  
G. Balakrish Nair ◽  
Manikuntala Kundu
Keyword(s):  
Vibrio Cholerae ◽  
Target Gene ◽  
Target Genes ◽  
Gene Mutations ◽  
Proton Motive Force ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Active Efflux

ABSTRACT Quinolones are among the drugs of choice in the management of cholera caused by Vibrio cholerae. In this study, we demonstrate that, in addition to mutations detected in the target genes gyrA and parC, proton motive force-dependent efflux is involved in quinolone resistance in clinical isolates of V. cholerae.

scholarly journals Genetic Evidence for a Protein Kinase A/Cubitus Interruptus Complex That Facilitates Processing of Cubitus Interruptus in Drosophila

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1157-1166
Author(s):  
John A Kiger ◽  
Cristin O'Shea
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Target Gene ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Cubitus Interruptus ◽  
Mutant Forms ◽  
The Relationship ◽  
Kinase A

Abstract Hedgehog (Hh) activates a signal transduction pathway regulating Cubitus interruptus (Ci). In the absence of Hh, full-length Ci (Ci-155) is bound in a complex that includes Costal2 (Cos2) and Fused (Fu). Ci-155 is phosphorylated by protein kinase A (PKA), inducing proteolysis to Ci-75, a transcriptional repressor. Hh signaling blocks proteolysis and produces an activated Ci-155 transcriptional activator. The relationship between PKA and the Ci/Cos2/Fu complex is unclear. Here we examine Hh target gene expression caused by mutant forms of PKA regulatory (PKAr) and catalytic (PKAc) subunits and by the PKAc inhibitor PKI(1-31). The mutant PKAr*, defective in binding cAMP, is shown to activate Hh target genes solely through its ability to bind and inhibit endogenous PKAc. Surprisingly, PKAcA75, a catalytically impaired mutant, also activates Hh target genes. To account for this observation, we propose that PKAc phosphorylation targeting Ci-155 for proteolysis is regulated within a complex that includes PKAc and Ci-155 and excludes PKI(1-31). This complex may permit processive phosphorylation of Ci-155 molecules, facilitating their processing to Ci-75.

Cubitus interruptus-independent transduction of the Hedgehog signal in Drosophila

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5509-5522 ◽  
Author(s):  
A. Gallet ◽  
C. Angelats ◽  
S. Kerridge ◽  
P.P. Therond
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Drosophila Embryo ◽  
Key Factors ◽  
Cubitus Interruptus ◽  
Finger Protein ◽  
Control Pattern ◽  
Hedgehog Signal

The Hedgehog (Hh) family of secreted proteins are key factors that control pattern formation in invertebrates and vertebrates. The manner in which Hh molecules regulate a target cell remains poorly understood. In the Drosophila embryo, Hh is produced in identical stripes of cells in the posterior compartment of each segment. From these cells a Hh signal acts in both anterior and posterior directions. In the anterior cells, the target genes wingless and patched are activated whereas posterior cells respond to Hh by expressing rhomboid and patched. Here, we have examined the role of the transcription factor Cubitus interruptus (Ci) in this process. So far, Ci has been thought to be the most downstream component of the Hh pathway capable of activating all Hh functions. However, our current study of a null ci allele, indicates that it is actually not required for all Hh functions. Whereas Hh and Ci are both required for patched expression, the target genes wingless and rhomboid have unequal requirements for Hh and Ci activity. Hh is required for the maintenance of wingless expression before embryonic stage 11 whereas Ci is necessary only later during stage 11. For rhomboid expression Hh is required positively whereas Ci exhibits negative input. These results indicate that factors other than Ci are necessary for Hh target gene regulation. We present evidence that the zinc-finger protein Teashirt is one candidate for this activity. We show that it is required positively for rhomboid expression and that Teashirt and Ci act in a partially redundant manner before stage 11 to maintain wingless expression in the trunk.

scholarly journals Interleukin-6-induced serine phosphorylation of transcription factor APRF: evidence for a role in interleukin-6 target gene induction

FEBS Letters ◽  
1995 ◽  
Vol 360 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Claudia Lütticken ◽  
Paul Coffer ◽  
Juping Yuan ◽  
Claudia Schwartz ◽  
Eric Caldenhoven ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Interleukin 6 ◽  
Target Gene ◽  
Gene Induction ◽  
Serine Phosphorylation ◽  
Target Gene Induction

scholarly journals Role of the Nrf2-ARE Pathway in Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Mi Shin ◽  
Ji Hye Yang ◽  
Sung Hwan Ki
Keyword(s):  
Liver Diseases ◽  
Target Genes ◽  
Antioxidant Response ◽  
Related Factor ◽  
Genes Expression ◽  
Wide Range ◽  
Range Of Functions ◽  
Central Organ ◽  
Essential Transcription Factor

The liver is a central organ that performs a wide range of functions such as detoxification and metabolic homeostasis. Since it is a metabolically active organ, liver is particularly susceptible to oxidative stress. It is well documented that liver diseases including hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are highly associated with antioxidant capacity. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. It is activated in response to electrophiles and induces its target genes by binding to the antioxidant response element (ARE). Therefore, the roles of the Nrf2-ARE pathway in liver diseases have been extensively investigated. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis, alcoholic and nonalcoholic liver disease, fibrosis, and cancer via target gene expression. In this review, we will discuss the role of the Nrf2-ARE pathway in liver pathophysiology and the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.

scholarly journals Hsa-circ-0064636 regulation of the target gene VDAC1/UBE4A by hsa-miR-326/hsa-miR-503-5 in osteosarcoma

2021 ◽  
Author(s):  
Guohua Yan ◽  
Hanji Huang ◽  
Kanglu Li ◽  
Mingjun Zheng ◽  
Jiagang Qin ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Target Gene ◽  
Target Genes ◽  
Gene Prediction ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Circular Rnas ◽  
Qrt Pcr ◽  
Eukaryotic Organisms

Abstract Background: Circular RNAs (circRNAs) are a subclass of noncoding RNAs that play a critical role in the regulation of gene expression in eukaryotic organisms. Recent studies have revealed the critical role of circRNAs in cancer progression. Yet, little is not well understood of hsa-circ-0064636 in osteosarcoma (OS).Methods: The differential expression of hsa-circ-0064636 in OS cell lines was verified by quantitative real-time PCR (qRT-PCR). Differentially expressed mRNAs and miRNAs were screened in OS mRNA and miRNA expression datasets. miRNAs that interacted with hsa-circ-0064636 were predicted by RNAhybrid, TargetScan and miRanda. and were further detected using RNAhybrid, TargetScan and miRanda. miRWalk, miRMap, and miRNAMap were used to perform target gene prediction on the intersected miRNAs to construct a circ-miRNA-mRNA interactor network. The target genes were then subjected to survival analysis using PROGgeneV2, which resulted in a circ-miRNA-mRNA interaction subnetwork with prognostic impact.Results: The qRT-PCR experiments successfully verified that hsa-circ-0064636 was significantly overexpressed in the OS cell line. Hsa-mir-326(miR-326) and hsa-mir-503-5p(miR-503-5p) are target miRNAs of hsa-circ-0064636 in the target genes obtained from the miR-326 and miR-503-5p screens. UBE4A and VDAC1 had a significant effect on prognosis. UBE4A is a target gene for miR-326, while VDAC1 is a target gene for miR-503-5p .Conclusion: hsa-circ-0064636 may be involved in OS development through acting as a sponge to inhibit miR-326 and miR-503-5p , thus regulating the expression of VDAC1 and UBE4A.

scholarly journals Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Karan Naresh Amin ◽  
Palanisamy Rajagru ◽  
Koustav Sarkar ◽  
M. R. Ganesh ◽  
Takayoshi Suzuki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Target Genes ◽  
Defense Mechanism ◽  
Redox Homeostasis ◽  
Related Factor ◽  
Protective Mechanisms ◽  
Nrf2 Activator

Endoplasmic reticulum (ER) plays a key role in the folding, modification, and trafficking of proteins. When the homeostasis of the ER is disturbed, un/misfolded proteins accumulate in the ER which leads to ER stress. Sustained ER stress results in apoptosis, which is associated with various diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor in redox homeostasis by regulating various genes associated with detoxification and cell-protective mechanisms. We found that Rosolic acid (RA) treatment dose-dependently activates Nrf2 in endothelial cells using the enzyme fragment complementation assay. The cytoprotective role of RA against ER stress-induced endothelial apoptosis and its molecular mechanism was explored in the present study. The Nrf2 and its target genes, as well as ER stress marker expressions, were measured by qPCR in ER stress-exposed endothelial cells. The contribution of Nrf2 in RA-mediated defense mechanism in endothelial cells was established by knockout studies using Nrf2-CRISPR/Cas9. The treatment with RA to ER stress-induced endothelial cells exhibited activation of Nrf2, as demonstrated by Nrf2 translocation and reduction of ER stress markers. We found that the Nrf2 knockout sensitized the endothelial cells against ER stress, and further, RA failed to mediate its cytoprotective effect. Proteomic studies using LC-MS/MS revealed that among the 1370 proteins detected, we found 296 differentially regulated proteins in ER stress-induced endothelial cells, and RA administration ameliorated 71 proteins towards the control levels. Of note, the ER stress in endothelial cells was attenuated by the treatment with the RA, suggesting the role of the Nrf2 activator in the pathological conditions of ER stress-associated diseases.

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