Domains Formed within the N-terminal Region of the Quorumsensing Activator TraR Are Required for Transcriptional Activation and Direct Interaction with RpoA fromAgrobacterium

ABSTRACT Constitutive levels of production of STAT-1 were reduced by 10 h postinfection (p.i.) and significantly lost by 24 h p.i. in FL cells acutely infected with mumps virus (MuV). This result was consistent with that observed in previous studies and experiments with cells persistently infected with MuV (FLMT cells). There was a marked decrease in the amount of STAT-1 in cells expressing MuV accessory protein V (MuV-V). Furthermore, single amino acid substitutions in the Cys-rich region of V protein (Vc189a, Vc207a, and Vc214a) showed that each cysteine residue plays an important role in the decrease in STAT-1 production, but substitution of a histidine residue at amino acid position 203 had no effect. These events and the resultant suppression of the alpha interferon (IFN-α) response were confirmed by a luciferase reporter gene assay with five tandem repeats of the IFN-α-stimulated response element as an enhancer element of the firely luciferase gene. STAT-1 production was restored and detectable in FLMT cells treated with a proteosome inhibitor, such as MG132 or lactacystin. In the presence of MG132, ubiquitination of STAT-1 and the interaction of MuV-V with STAT-1 were demonstrated in FLMT cells by immunoprecipitation with anti-STAT-1 antibody. The same results for the interaction and ubiquitination were obtained in experiments with an expression vector for a C-terminal deletion mutant of STAT-1. The truncated STAT-1 molecules were degraded in the presence of MuV-V. Therefore, the C-terminal region (transcriptional activation and Src homology 2 domains) of STAT-1 is not necessary for its degradation caused by MuV-V. Our data suggest that MuV-V promotes ubiquitination and degradation of STAT-1.

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CTRP9 Mediates Protective Effects in Cardiomyocytes via AMPK- and Adiponectin Receptor-Mediated Induction of Anti-Oxidant Response

Cells ◽

10.3390/cells9051229 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1229

Author(s):

Bernd Niemann ◽

Ling Li ◽

Dorothee Siegler ◽

Benedikt H. Siegler ◽

Fabienne Knapp ◽

...

Keyword(s):

Transcriptional Activation ◽

Direct Interaction ◽

Left Ventricular ◽

Cardiac Cells ◽

Adiponectin Receptor ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Anti Oxidant ◽

Cardioprotective Effects ◽

The Right

The C1q/tumor necrosis factor-alpha-related protein 9 (CTRP9) has been reported to exert cardioprotective effects, but its role in the right ventricle (RV) remains unclear. To investigate the role of CTRP9 in RV hypertrophy and failure, we performed pulmonary artery banding in weanling rats to induce compensatory RV hypertrophy seven weeks after surgery and RV failure 22 weeks after surgery. CTRP9 expression, signal transduction and mechanisms involved in protective CTRP9 effects were analyzed in rat and human RV tissue and cardiac cells. We demonstrate that CTRP9 was induced during compensatory RV hypertrophy but almost lost at the stage of RV failure. RV but not left ventricular (LV) cardiomyocytes or RV endothelial cells demonstrated increased intracellular reactive oxygen species (ROS) and apoptosis activation at this stage. Exogenous CTRP9 induced AMP-activated protein kinase (AMPK)-dependent transcriptional activation of the anti-oxidant thioredoxin-1 (Trx1) and superoxide dismutase-2 (SOD2) and reduced phenylephrine-induced ROS. Combined knockdown of adiponectin receptor-1 (AdipoR1) and AdipoR2 or knockdown of calreticulin attenuated CTRP9-mediated anti-oxidant effects. Immunoprecipitation showed an interaction of AdipoR1 with AdipoR2 and the co-receptor T-cadherin, but no direct interaction with calreticulin. Thus, CTRP9 mediates cardioprotective effects through inhibition of ROS production induced by pro-hypertrophic agents via AMPK-mediated activation of anti-oxidant enzymes.

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An Abf1p C-terminal region lacking transcriptional activation potential stimulates a yeast origin of replication

Nucleic Acids Research ◽

10.1093/nar/25.21.4250 ◽

1997 ◽

Vol 25 (21) ◽

pp. 4250-4256 ◽

Cited By ~ 13

Author(s):

S. Wiltshire ◽

S. Raychaudhuri ◽

S. Eisenberg

Keyword(s):

Transcriptional Activation ◽

Terminal Region ◽

Origin Of Replication ◽

Activation Potential

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Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors.

Molecular and Cellular Biology ◽

10.1128/mcb.15.2.943 ◽

1995 ◽

Vol 15 (2) ◽

pp. 943-953 ◽

Cited By ~ 570

Author(s):

R I Scheinman ◽

A Gualberto ◽

C M Jewell ◽

J A Cidlowski ◽

A S Baldwin

Keyword(s):

Gene Expression ◽

Hela Cells ◽

Transcriptional Activation ◽

Glucocorticoid Receptors ◽

Interleukin 1 ◽

Direct Interaction ◽

Significant Loss ◽

Nf Kappa B ◽

Necrosis Factor Alpha ◽

Important Regulator

Glucocorticoids are potent immunosuppressants which work in part by inhibiting cytokine gene transcription. We show here that NF-kappa B, an important regulator of numerous cytokine genes, is functionally inhibited by the synthetic glucocorticoid dexamethasone (DEX). In transfection experiments, DEX treatment in the presence of cotransfected glucocorticoid receptor (GR) inhibits NF-kappa B p65-mediated gene expression and p65 inhibits GR activation of a glucocorticoid response element. Evidence is presented for a direct interaction between GR and the NF-kappa B subunits p65 and p50. In addition, we demonstrate that the ability of p65, p50, and c-rel subunits to bind DNA is inhibited by DEX and GR. In HeLa cells, DEX activation of endogenous GR is sufficient to block tumor necrosis factor alpha or interleukin 1 activation of NF-kappa B at the levels of both DNA binding and transcriptional activation. DEX treatment of HeLa cells also results in a significant loss of nuclear p65 and a slight increase in cytoplasmic p65. These data reveal a second mechanism by which NF-kappa B activity may be regulated by DEX. We also report that RU486 treatment of wild-type GR and DEX treatment of a transactivation mutant of GR each can significantly inhibit p65 activity. In addition, we found that the zinc finger domain of GR is necessary for the inhibition of p65. This domain is also required for GR repression of AP-1. Surprisingly, while both AP-1 and NF-kappa B can be inhibited by activated GR, synergistic NF-kappa B/AP-1 activity is largely unaffected. These data suggest that NF-kappa B, AP-1, and GR interact in a complex regulatory network to modulate gene expression and that cross-coupling of NF-kappa B and GR plays an important role in glucocorticoid-mediated repression of cytokine transcription.

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Characteristics and Expression Pattern of MYC Genes in Triticum aestivum, Oryza sativa, and Brachypodium distachyon

Plants ◽

10.3390/plants8080274 ◽

2019 ◽

Vol 8 (8) ◽

pp. 274 ◽

Cited By ~ 2

Author(s):

Shoukun Chen ◽

Hongyan Zhao ◽

Tengli Luo ◽

Yue Liu ◽

Xiaojun Nie ◽

...

Keyword(s):

Transcriptional Activation ◽

Leucine Zipper ◽

Brachypodium Distachyon ◽

Expression Patterns ◽

Terminal Region ◽

Gene Promoters ◽

Interaction Domain ◽

Specific Expression ◽

Systematic Analysis ◽

Transcriptional Activation Domain

Myelocytomatosis oncogenes (MYC) transcription factors (TFs) belong to basic helix-loop-helix (bHLH) TF family and have a special bHLH_MYC_N domain in the N-terminal region. Presently, there is no detailed and systematic analysis of MYC TFs in wheat, rice, and Brachypodium distachyon. In this study, 26 TaMYC, 7 OsMYC, and 7 BdMYC TFs were identified and their features were characterized. Firstly, they contain a JAZ interaction domain (JID) and a putative transcriptional activation domain (TAD) in the bHLH_MYC_N region and a BhlH region in the C-terminal region. In some cases, the bHLH region is followed by a leucine zipper region; secondly, they display tissue-specific expression patterns: wheat MYC genes are mainly expressed in leaves, rice MYC genes are highly expressed in stems, and B. distachyon MYC genes are mainly expressed in inflorescences. In addition, three types of cis-elements, including plant development/growth-related, hormone-related, and abiotic stresses-related were identified in different MYC gene promoters. In combination with the previous studies, these results indicate that MYC TFs mainly function in growth and development, as well as in response to stresses. This study laid a foundation for the further functional elucidation of MYC genes.

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Role of the N-terminal region of Rap1p in the transcriptional activation of glycolytic genes inSaccharomyces cerevisiae

Yeast ◽

10.1002/yea.1123 ◽

2004 ◽

Vol 21 (10) ◽

pp. 851-866 ◽

Cited By ~ 16

Author(s):

Takayuki Mizuno ◽

Tomoko Kishimoto ◽

Tomoko Shinzato ◽

Robin Haw ◽

Alistair Chambers ◽

...

Keyword(s):

Transcriptional Activation ◽

Terminal Region

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Transcriptional Activation by STAT6 Requires the Direct Interaction with NCoA-1

Journal of Biological Chemistry ◽

10.1074/jbc.m108132200 ◽

2001 ◽

Vol 276 (49) ◽

pp. 45713-45721 ◽

Cited By ~ 52

Author(s):

Claudia M. Litterst ◽

Edith Pfitzner

Keyword(s):

Transcriptional Activation ◽

Direct Interaction

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Recruitment of CBP/p300, TATA-Binding Protein, and S8 to Distinct Regions at the N Terminus of Adenovirus E1A

Journal of Virology ◽

10.1128/jvi.79.9.5594-5605.2005 ◽

2005 ◽

Vol 79 (9) ◽

pp. 5594-5605 ◽

Cited By ~ 32

Author(s):

Mozhgan Rasti ◽

Roger J. A. Grand ◽

Joe S. Mymryk ◽

Phillip H. Gallimore ◽

Andrew S. Turnell

Keyword(s):

Transcriptional Activation ◽

Binding Sites ◽

Transcriptional Repression ◽

Binding Protein ◽

Cellular Transformation ◽

Tata Binding Protein ◽

Transformation Process ◽

Terminal Region ◽

Site Directed Mutagenesis

ABSTRACT The N-terminal region of the adenovirus (Ad) 12S E1A gene product targets several cellular proteins that are essential for the induction of S phase, cellular immortalization, cellular transformation, transcriptional repression, and transcriptional activation. The precise binding sites for these proteins, however, remain to be resolved. We therefore undertook an extensive site-directed mutagenesis approach to generate specific point mutants and to precisely map the binding sites for CBP, p300, TATA-binding protein (TBP), S4, S8, hGcn5, P/CAF, and Ran within the first 30 amino acids of the Ad5 12S E1A protein. We determined that although common residues within the N-terminal region can form partial binding sites for these proteins, point mutants were also generated that could discriminate between binding sites. These data indicate that AdE1A can target each of these proteins individually through distinct binding sites. It was evident, however, that the mutation of specific hydrophobic residues typically had the greatest effect upon AdE1A's ability to bind individual partners. Indeed, the mutation of L at positions 19 and 20 eliminated the ability of AdE1A to interact with any of the N-terminal binding proteins studied here. Interestingly, although TBP and S8 or CBP/p300 can exist as functional complexes, RNA interference revealed that the recruitment of either TBP, S8, or CBP/p300 to AdE1A was not dependent upon the expression of the other proteins. These data further indicate that AdE1A can target individual partner proteins in vivo and that it does not necessarily recruit these proteins indirectly as components of larger macromolecular complexes. Finally, we took advantage of the fine-mapping data to ascertain which proteins were targeted during the transformation process. Consistent with previous studies, CBP/p300 was found to be targeted by AdE1A during this process, although our data suggest that binding to other N-terminal proteins is also important for transformation.

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A 10-amino-acid sequence in the N-terminal A/B domain of thyroid hormone receptor alpha is essential for transcriptional activation and interaction with the general transcription factor TFIIB.

Molecular and Cellular Biology ◽

10.1128/mcb.15.8.4507 ◽

1995 ◽

Vol 15 (8) ◽

pp. 4507-4517 ◽

Cited By ~ 79

Author(s):

E Hadzic ◽

V Desai-Yajnik ◽

E Helmer ◽

S Guo ◽

S Wu ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Thyroid Hormone ◽

Dna Binding ◽

Transcriptional Activation ◽

Thyroid Hormone Receptor ◽

Alpha Helix ◽

Binding Domain ◽

Terminal Region ◽

Binding Studies

The effects of the thyroid hormone (3,5,3'-triiodo-L-thyronine [T3]) on gene transcription are mediated by nuclear T3 receptors (T3Rs). alpha- and beta-isoform T3Rs (T3R alpha and -beta) are expressed from different genes and are members of a superfamily of ligand-dependent transcription factors that also includes the receptors for steroid hormones, vitamin D, and retinoids. Although T3 activates transcription by mediating a conformational change in the C-terminal approximately 220-amino-acid ligand-binding domain (LBD), the fundamental mechanisms of T3R-mediated transcriptional activation remain to be determined. We found that deletion of the 50-amino-acid N-terminal A/B domain of chicken T3R alpha (cT3R alpha) decreases T3-dependent stimulation of genes regulated by native thyroid hormone response elements about 10- to 20-fold. The requirement of the A/B region for transcriptional activation was mapped to amino acids 21 to 30, which contain a cluster of five basic amino acids. The A/B region of cT3R alpha is not required for T3 binding or for DNA binding of the receptor as a heterodimer with retinoid X receptor. In vitro binding studies indicate that the N-terminal region of cT3R alpha interacts efficiently with TFIIB and that this interaction requires amino acids 21 to 30 of the A/B region. In contrast, the LBD interacts poorly with TFIIB. The region of TFIIB primarily involved in the binding of cT3R alpha includes an amphipathic alpha helix contained within residues 178 to 201. Analysis using a fusion protein containing the DNA-binding domain of GAL4 and the entire A/B region of cT3R alpha suggests that this region does not contain an intrinsic activation domain. These and other studies indicate that cT3R alpha mediates at least some of its effects through TFIIB in vivo and that the N-terminal region of DNA-bound cT3R alpha acts to recruit and/or stabilize the binding of TFIIB to the transcription complex. T3 stimulation could then result from ligand-mediated changes in the LBD which may lead to the interaction of other factors with cT3R alpha, TFIIB, and/or other components involved in the initiation of transcription.

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