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"Ap-1 binding site"

Gerald Thiel, Oliver G Rössler
Hypericum perforatum is one of the most prominent medical plants. Hyperforin, a main ingredient of H. perforatum, has been shown to activate transient receptor potential canonical C6 (TRPC6) channels. Alternatively, it has been proposed that hyperforin functions as a protonophore in a TRPC6-independent manner. Here, we show that hyperforin stimulation activates the transcription factor AP-1 in HEK293 cells expressing TRPC6 (T6.11 cells), but did not substantially change the AP-1 activity in HEK293 cells lacking TRPC6...
January 19, 2017: Biochemical Pharmacology
Y-H Liao, K-H Chiang, J-M Shieh, C-R Huang, C-J Shen, W-C Huang, B-K Chen
Epidermal growth factor (EGF) is important for cancer cell proliferation, angiogenesis and metastasis in many types of cancer. However, the mechanisms involved in EGF-induced head and neck squamous cell carcinoma (HNSCC) metastasis remain largely unknown. In this study, we reveal that angiopoietin-like 4 (ANGPTL4) plays an important role in the regulation of EGF-induced cancer metastasis. We showed that EGF-induced ANGPTL4 expression promoted anoikis resistance and cancer cell migration and invasion in HNSCC...
October 31, 2016: Oncogene
Ekaterina Dimitrova Bojilova, Christine Weyn, Marie-Hélène Antoine, Véronique Fontaine
Histone deacetylase inhibitors (HDACi) have been shown to render HPV-carrying cells susceptible to intrinsic and extrinsic apoptotic signals. As such, these epigenetic drugs have entered clinical trials in the effort to treat cervical cancer. Here, we studied the effect of common HDACi, with an emphasis on Trichostatin A (TSA), on the transcriptional activity of the HPV-16 Long Control Region (LCR) in order to better understand the impact of these agents in the context of the HPV life cycle and infection. HDACi strongly induced transcription of the firefly luciferase reporter gene under the control of the HPV-16 LCR in a variety of cell lines...
September 26, 2016: Oncotarget
Weilong Yao, You-Take Oh, Jiusheng Deng, Ping Yue, Liang Deng, Henry Huang, Wei Zhou, Shi-Yong Sun
Death receptor 4 (DR4) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling is a well known and the best-studied effector pathway downstream of Ras and Raf. This study focuses on determining the impact of pharmacological MEK inhibition on DR4 expression and elucidating the underlying mechanism. We found that several MEK inhibitors including MEK162, AZD6244, and PD0325901 effectively decreased DR4 protein levels including cell surface DR4 in different cancer cell lines...
October 7, 2016: Journal of Biological Chemistry
Jing Lu, Jia-Hui Guo, Xue-Liang Tu, Chao Zhang, Mei Zhao, Quan-Wu Zhang, Feng-Hou Gao
Recent research found that Tiron was an effective antioxidant that could act as the intracellular reactive oxygen species (ROS) scavenger or alleviate the acute toxic metal overload in vivo. In this study, we investigated the inhibitory effect of Tiron on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human dermal fibroblast cells. Western blot and ELISA analysis revealed that Tiron inhibited ultraviolet B (UVB)-induced protein expression of MMP-1 and MMP-3. Real-time quantitative PCR confirmed that Tiron could inhibit UVB-induced mRNA expression of MMP-1 and MMP-3...
2016: PloS One
Karmel A Allison, Eniko Sajti, Jana G Collier, David Gosselin, Ty Dale Troutman, Erica L Stone, Stephen M Hedrick, Christopher K Glass
Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites...
July 4, 2016: ELife
Yuguang Liang, Junlan Zhu, Haishan Huang, Daimin Xiang, Yang Li, Dongyun Zhang, Jingxia Li, Yulei Wang, Honglei Jin, Guosong Jiang, Zeyuan Liu, Chuanshu Huang
Isorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells...
August 2, 2016: Autophagy
Laure Blatti-Cardinaux, Leticia Sanjosé, Marie-Luise Zahno, Reto Zanoni, Ramses Reina, Giuseppe Bertoni
In spite of an eradication campaign that eliminated clinical cases of caprine arthritis encephalitis virus-induced arthritis in the Swiss goat population, seroconversions are still observed. In the affected flocks, viruses belonging mainly to the small ruminant lentivirus A4 subtype are regularly isolated. These viruses are considered attenuated, except in the mammary gland, where high viral loads and histopathological lesions have been observed. We previously characterized and sequenced such field isolates, detecting several potentially attenuating mutations in their LTR...
July 2016: Journal of General Virology
Mohamed Mahmoud M Abdel-Latif, Hiroyasu Inoue, Dermot Kelleher, John V Reynolds
AIMS: Gastroesophageal reflux disease is considered to be a major risk in the development of esophageal adenocarcinoma. Nuclear factor-kappa B (NF-κB) plays important roles in the regulation of several genes coding for cytokines, cell proliferation, and apoptosis. To understand the role of bile and acid in the causation of esophageal cancer, we have examined the effects of bile acids and acid on NF-κB activation in the esophageal epithelial cells OE33 and SKGT-4 qualitatively and quantitatively...
January 2016: Journal of Cancer Research and Therapeutics
Adam W Turner, Amy Martinuk, Anada Silva, Paulina Lau, Majid Nikpay, Per Eriksson, Lasse Folkersen, Ljubica Perisic, Ulf Hedin, Sebastien Soubeyrand, Ruth McPherson
OBJECTIVE: A recent genome-wide association study meta-analysis identified an intronic single nucleotide polymorphism in SMAD3, rs56062135C>T, the minor allele (T) which associates with protection from coronary artery disease. Relevant to atherosclerosis, SMAD3 is a key contributor to transforming growth factor-β pathway signaling. Here, we seek to identify ≥1 causal coronary artery disease-associated single nucleotide polymorphisms at the SMAD3 locus and characterize mechanisms whereby the risk allele(s) contribute to coronary artery disease risk...
May 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Steve J Morrissy, Haipeng Sun, Jack Zhang, Joshua Strom, Qin M Chen
Corticosterone (CT), progesterone (PG), and retinoic acid (RA) are capable of inhibiting Doxorubicin (Dox) from inducing apoptosis in rat cardiomyocytes. Mechanistically, CT, PG, and RA induce increases of Bcl-xL protein and mRNA, and activate a 3.2 kb bcl-x gene promoter. CT and RA, but not PG, induced the activity of a 0.9 kb bcl-x promoter, containing sequences for AP-1 and NF-kB binding. RA, but not CT or PG, induced NF-kB activation. CT, but not PG or RA, induced AP-1 activation, and induction of the 0...
June 2016: Journal of Biochemical and Molecular Toxicology
Yahui Zhao, Aiping Luo, Sheng Li, Wei Zhang, Hongyan Chen, Yi Li, Fang Ding, Furong Huang, Zhihua Liu
ID1 (inhibitor of differentiation/DNA binding 1) acts an important role in metastasis, tumorigenesis, and maintenance of cell viability. It has been shown that the up-regulation of ID1 is correlated with poor prognosis and the resistance to chemotherapy of human cancers. However, the underlying molecular mechanism remains elusive. Here, we determined for the first time that up-regulating ID1 upon etoposide activation was mediated through AP-1 binding sites within theID1promoter and confirmed that ID1 enhanced cell resistance to DNA damage-induced apoptosis in esophageal squamous cell carcinoma cells...
March 25, 2016: Journal of Biological Chemistry
Maria Delcuratolo, Jasmin Fertey, Markus Schneider, Johanna Schuetz, Natalie Leiprecht, Benjamin Hudjetz, Stephan Brodbeck, Silke Corall, Marcel Dreer, Roxana Michaela Schwab, Martin Grimm, Shwu-Yuan Wu, Frank Stubenrauch, Cheng-Ming Chiang, Thomas Iftner
We investigated the mechanism of how the papillomavirus E2 transcription factor can activate promoters through activator protein (AP)1 binding sites. Using an unbiased approach with an inducible cell line expressing the viral transcription factor E2 and transcriptome analysis, we found that E2 induces the expression of the two AP1 components c-Fos and FosB in a Brd4-dependent manner. In vitro RNA interference confirmed that c-Fos is one of the AP1 members driving the expression of viral oncogenes E6/E7. Mutation analysis and in vivo RNA interference identified an essential role for c-Fos/AP1 and also for the bromodomain protein Brd4 for papillomavirus-induced tumorigenesis...
January 2016: PLoS Pathogens
Nallani Vijay Kumar, Jianbo Yang, Jitesh K Pillai, Swati Rawat, Carlos Solano, Abhay Kumar, Morten Grøtli, Timothy L Stemmler, Barry P Rosen, Markus J Tamás
The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274...
March 2016: Molecular and Cellular Biology
Markus J Harder, Markus Anliker, Britta Höchsmann, Thomas Simmet, Markus Huber-Lang, Hubert Schrezenmeier, Daniel Ricklin, John D Lambris, Paul N Barlow, Christoph Q Schmidt
The serum proteins factor H (FH), consisting of 20 complement control protein modules (CCPs), and its splice product FH-like protein 1 (FHL-1; consisting of CCPs 1-7) are major regulators of the alternative pathway (AP) of complement activation. The engineered version of FH, miniFH, contains only the N- and C-terminal portions of FH linked by an optimized peptide and shows ∼ 10-fold higher ex vivo potency. We explored the hypothesis that regulatory potency is enhanced by unmasking of a ligand-binding site in the C-terminal CCPs 19-20 that is cryptic in full-length native FH...
January 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
I V Zueva, V E Semenov, M A Mukhamedyarov, S V Lushchekina, A D Kharlamova, E O Petukhova, A S Mikhailov, S N Podyachev, L F Saifina, K A Petrov, O A Minnekhanova, V V Zobov, E E Nikolsky, P Masson, V S Reznik
BACKGROUND: Alzheimer's disease (AD) is the major age-related progressive neurodegenerative disorder. The brain of AD patients suffers from loss of cholinergic neurons and decreased number of synapses [1]. AD is caused by an imbalance between Aβ production and clearance, resulting in increased amount of Aβ in various forms [2]. Reduction of Aβ production and increasing clearance of Aβ pathogenic forms are key targets in the development of potential therapeutic agents for AD treatment...
2015: International Journal of Risk & Safety in Medicine
Yair Glick, Yaron Orenstein, Dana Chen, Dorit Avrahami, Tsaffrir Zor, Ron Shamir, Doron Gerber
Protein binding to DNA is a fundamental process in gene regulation. Methodologies such as ChIP-Seq and mapping of DNase I hypersensitive sites provide global information on this regulation in vivo In vitro methodologies provide valuable complementary information on protein-DNA specificities. However, current methods still do not measure absolute binding affinities. There is a real need for large-scale quantitative protein-DNA affinity measurements. We developed QPID, a microfluidic application for measuring protein-DNA affinities...
April 7, 2016: Nucleic Acids Research
Yu-Wen Chu, Shu-Ting Liu, Hsiao-Chun Cheng, Shih-Ming Huang, Yung-Lung Chang, Chien-Ping Chiang, Ying-Chun Liu, Wei-Ming Wang
ZAC, an encoding gene mapped at chromosome 6q24-q25 within PSORS1, was previously found over-expressed in the lower compartment of the hyperplastic epidermis in psoriatic lesions. Cytokines produced in the inflammatory dermatoses may drive AP-1 transcription factor to induce responsive gene expressions. We demonstrated that mZac1 can enhance AP-1-responsive S100A7 expression of which the encoding gene was located in PSORS4 with HaCaT keratinocytes. However, the mZac1-enhanced AP-1 transcriptional activity was suppressed by curcumin, indicating the anti-inflammatory property of this botanical agent and is exhibited by blocking the AP-1-mediated cross-talk between PSORS1 and PSORS4...
2015: PloS One
Yiwei Liu, Lingxin Zhang, Chuan Wang, Shama Roy, Jianzhong Shen
We recently reported that the P2Y2 receptor (P2Y2R) is the predominant nucleotide receptor expressed in human coronary artery endothelial cells (HCAEC) and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), a key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here, we report the role of a newly identified AP-1 consensus sequence in the TF gene promoter and its original binding components in P2Y2R regulation of TF transcription...
January 22, 2016: Journal of Biological Chemistry
Nam-Chul Cho, Ji Hyoun Cha, Hyojin Kim, Jinsook Kwak, Dohee Kim, Seung-Hwan Seo, Ji-Sun Shin, TaeHun Kim, Ki Duk Park, Jiyoun Lee, Kyoung Tai No, Yun Kyung Kim, Kyung-Tae Lee, Ae Nim Pae
Protease-activated receptor 2 (PAR2) is a member of G protein-coupled receptor and its activation initiates diverse inflammatory responses. Recent studies suggest that antagonists of PAR2 may provide a novel therapeutic strategy for inflammatory diseases. In this study, we have developed a series of 2-aryloxy-4-amino-quinazoline derivatives as PAR2 antagonists and examined their effects against LPS-induced inflammatory responses in RAW 264.7 macrophages. Among these derivatives, compound 2f displayed the greatest antagonistic activity with the IC50 value of 2...
December 15, 2015: Bioorganic & Medicinal Chemistry
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