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https://www.readbyqxmd.com/read/29321817/enhanced-myc-association-with-the-nua4-histone-acetyltransferase-complex-mediated-by-the-adenovirus-e1a-n-terminal-domain-activates-a-subset-of-myc-target-genes-highly-expressed-in-cancer-cells
#1
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The proto-oncogene MYC is a transcription factor over-expressed in many cancers and required for cell survival. Its function is regulated by histone acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60 complex. However, the roles of the HAT complexes during MYC function in cancer have not been well characterized. We recently showed that adenovirus E1A and its N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4 complex...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29241042/the-adenovirus-e1a-c-terminus-suppresses-a-delayed-antiviral-response-and-modulates-ras-signaling
#2
Nathan R Zemke, Arnold J Berk
The N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress innate immune responses and force host cells into S-phase. In contrast, the functions of e1a's C-terminal interactions with FOXK, DCAF7, and CtBP are unknown. We found that these interactions modulate RAS signaling, and that a single e1a molecule must bind all three of these host proteins to suppress activation of a subset of IFN-stimulated genes (ISGs). These ISGs were otherwise induced in primary respiratory epithelial cells at 12 hr p...
December 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29238045/ripk3-promotes-adenovirus-type-5-activity
#3
Melanie Weigert, Alex Binks, Suzanne Dowson, Elaine Y L Leung, Dmitris Athineos, Xinzi Yu, Margaret Mullin, Josephine B Walton, Clare Orange, Darren Ennis, Karen Blyth, Stephen W G Tait, Iain A McNeish
Oncolytic adenoviral mutants infect human malignant cells and replicate selectively within them. This induces direct cytotoxicity that can also trigger profound innate and adaptive immune responses. However, the mechanism by which adenoviruses produce cell death remains uncertain. We previously suggested that type 5 adenoviruses, including the E1A CR2 deletion mutant dl922-947, might induce a novel form of programmed death resembling necroptosis. Here we have investigated the roles of core necrosis proteins RIPK1, RIPK3 and MLKL in the cytotoxicity of dl922-947 and other adenovirus serotypes...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29228615/combined-therapy-of-colon-carcinomas-with-an-oncolytic-adenovirus-and-valproic-acid
#4
Christian Bressy, Dragomira Majhen, Najat Raddi, Wael Jdey, Gaétan Cornilleau, Léna Zig, Josée Guirouilh-Barbat, Bernard S Lopez, Olivia Bawa, Paule Opolon, Elodie Grellier, Karim Benihoud
The anti-tumor potential of oncolytic adenoviruses (CRAds) has been demonstrated in preclinical and clinical studies. While these agents failed to eradicate tumors when used as a monotherapy, they may be more effective if combined with conventional treatments such as radiotherapy or chemotherapy. This study seeks to evaluate the combination of a CRAd bearing a ∆24 deletion in E1A with valproic acid (VPA), a histone deacetylase inhibitor, for the treatment of human colon carcinomas. This combination led to a strong inhibition of cell growth both in vitro and in vivo compared to treatment with CRAd or VPA alone...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163768/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#5
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#6
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29140794/targeted-elimination-of-senescent-ras-transformed-cells-by-suppression-of-mek-erk-pathway
#7
Elena Y Kochetkova, Galina I Blinova, Olga A Bystrova, Marina G Martynova, Valery A Pospelov, Tatiana V Pospelova
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras-transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition...
November 14, 2017: Aging
https://www.readbyqxmd.com/read/29126418/an-image-cytometric-technique-is-a-concise-method-to-detect-adenoviruses-and-host-cell-proteins-and-to-monitor-the-infection-and-cellular-responses-induced
#8
Takao Morinaga, Thảo Thi Thanh Nguyễn, Boya Zhong, Michiko Hanazono, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Masatoshi Tagawa
BACKGROUND: Genetically modified adenoviruses (Ad) with preferential replications in tumor cells have been examined for a possible clinical applicability as an anti-cancer agent. A simple method to detect viral and cellular proteins is valuable to monitor the viral infections and to predict the Ad-mediated cytotoxicity. METHODS: We used type 5 Ad in which the expression of E1A gene was activated by 5'-regulatory sequences of genes that were augmented in the expression in human tumors...
November 10, 2017: Virology Journal
https://www.readbyqxmd.com/read/29115418/predicting-pathogenic-genes-for-primary-myelofibrosis-based-on-a-system%C3%A2-network-approach
#9
Shu-Cai Xu, Peng Ning
The aim of the present study was to predict pathogenic genes for primary myelofibrosis (PMF) using a system‑network approach by combining protein‑protein interaction (PPI) network and gene expression data with known pathogenic genes. PMF gene expression profiles, known pathogenic genes and protein‑protein interactions were obtained. Using these data, differentially expressed genes (DEGs) were identified between PMF and normal conditions using significance analysis of microarrays, and seed genes were determined based on the intersection of known pathogenic genes and the PMF gene expression profile...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109020/an-immortalized-microglial-cell-line-mocha-derived-from-rat-cochlea
#10
G M Seigel, S Manohar, Y Y Bai, D Ding, R Salvi
Microglia are glial-immune cells that are essential for the function and survival of the central nervous system. Microglia not only protect neural tissues from immunological insults, but also play a critical role in neural development and repair. However, little is known about the biology of microglia in the cochlea, the auditory portion of the inner ear. In this study, we detected TMEM119+, CD11b+, CD45+ and Iba1+ populations of cells in the rat cochlea, particularly in Rosenthal's canal, inner sulcus and stria vascularis...
November 3, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29100326/fiber-modified-hexon-chimeric-oncolytic-adenovirus-targeting-cancer-associated-fibroblasts-inhibits-tumor-growth-in-gastric-carcinoma
#11
Tao Pang, Xinghua Wang, Jun Gao, Wei Chen, Xiao Jun Shen, Ming Ming Nie, Tianhang Luo, Kai Yin, Guoen Fang, Kai Xuan Wang, Xu Chao Xue
Objective: To evaluate the effects of fiber-modified hexon-chimeric recombinant oncolytic adenovirus targeting cancer associated fibroblasts (CAFs) on the gastric CAFs and the transplantation tumor mice model of gastric carcinoma (GC). Results: Compared with BJ cells and GPFs, the reproduction and infectivity of P9, P9-4C or GP adenoviruses were markedly higher in gastric CAFs. In addition, P9, P9-4C or GP had a significantly relatively more killing effect on gastric CAFs compared with GPFs, and have less oncolytic effect in BJ cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29075795/histone-acetyltransferase-p300-cbp-inhibitor-c646-blocks-the-survival-and-invasion-pathways-of-gastric-cancer-cell-lines
#12
Ya-Mei Wang, Meng-Li Gu, Fan-Sheng Meng, Wen-Rui Jiao, Xin-Xin Zhou, Hang-Ping Yao, Feng Ji
The histone acetyltransferases (HATs) adenovirus E1A-associated protein (p300) and CREB binding protein (CBP) serve as coactivators during a diverse assortment of cellular processes. In the present study, p300 and CBP were highly expressed in 5 gastric cancer (GC) cell lines (SGC‑7901, MKN45, MGC-803, BGC-823 and KATO III) compared with human normal gastric epithelial cell line (GES-1). C646, a selective inhibitor of p300 and CBP, inhibited cell viability and cell cycle and promoted cell apoptosis in all 5 GC cell lines...
October 23, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28965007/adenovirus-e1a-trrap-targeting-domain-mediated-enhancement-of-myc-association-with-the-nua4-complex-activates-a-panel-of-myc-target-genes-enriched-for-gene-expression-and-ribosome-biogenesis
#13
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
Cellular transformation by adenovirus E1A requires targeting TRRAP, a scaffold protein which helps assemble histone acetyltransferase complexes, including the NuA4 complex. We recently reported that E1A and E1A 1-80 (N-terminal 80 aa) promote association of the proto-oncogene product MYC with the NuA4 complex. The E1A N-terminal TRRAP-targeting (ET) domain is required for E1A 1-80 to interact with the NuA4 complex. We demonstrate that an ET-MYC fusion associates with the NuA4 complex more efficiently than does MYC alone...
December 2017: Virology
https://www.readbyqxmd.com/read/28935812/mir-130a-deregulates-pten-and-stimulates-tumor-growth
#14
Huijun Wei, Ri Cui, Julian Bahr, Nicola Zanesi, Zhenghua Luo, Wei Meng, Guang Liang, Carlo M Croce
H-RasV12 oncogene has been shown to promote autophagic cell death. Here, we provide evidence of a contextual role for H-RasV12 in cell death that is varied by its effects on miR-130a. In E1A-immortalized murine embryo fibroblasts, acute expression of H-RasV12 promoted apoptosis, but not autophagic cell death. miRNA screens in this system showed that miR-130a was strongly downregulated by H-RasV12 in this model system. Enforced expression of miR-130a increased cell proliferation in part via repression of PTEN...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28929492/potent-antitumor-effect-of-tumor-microenvironment-targeted-oncolytic-adenovirus-against-desmoplastic-pancreatic-cancer
#15
Yan Li, JinWoo Hong, Joung-Eun Oh, A-Rum Yoon, Chae-Ok Yun
Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT-driven transgene expression was highly cancer-specific and was superior to that of H(mT)E-driven expression...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28918031/anti-adenoviral-artificial-micrornas-expressed-from-aav9-vectors-inhibit-human-adenovirus-infection-in-immunosuppressed-syrian-hamsters
#16
Katrin Schaar, Anja Geisler, Milena Kraus, Sandra Pinkert, Markian Pryshliak, Jacqueline F Spencer, Ann E Tollefson, Baoling Ying, Jens Kurreck, William S Wold, Robert Klopfleisch, Karoly Toth, Henry Fechner
Infections of immunocompromised patients with human adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed Syrian hamsters...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28885709/prenylation-of-viral-proteins-by-enzymes-of-the-host-virus-driven-rationale-for-therapy-with-statins-and-ft-ggt1-inhibitors
#17
REVIEW
Ekaterina S Marakasova, Birgit Eisenhaber, Sebastian Maurer-Stroh, Frank Eisenhaber, Ancha Baranova
Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria...
September 8, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28874135/cytotoxicity-of-replication-competent-adenoviruses-powered-by-an-exogenous-regulatory-region-is-not-linearly-correlated-with-the-viral-infectivity-gene-expression-or-with-the-e1a-activating-ability-but-is-associated-with-the-p53-genotypes
#18
Suguru Yamauchi, Boya Zhong, Kiyoko Kawamura, Shan Yang, Shuji Kubo, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Masatoshi Tagawa
BACKGROUND: Replication-competent adenoviruses (Ad) produced cytotoxic effects on infected tumors and have been examined for the clinical applicability. A biomarkers to predict the cytotoxicity is valuable in a clinical setting. METHODS: We constructed type 5 Ad (Ad5) of which the expression of E1A gene was activated by a 5' regulatory sequences of survivin, midkine or cyclooxygenase-2, which were highly expressed in human tumors. We also produced the same replication-competent Ad of which the fiber-knob region was replaced by that of Ad35 (AdF35)...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28867494/targeting-human-breast-cancer-cells-by-an-oncolytic-adenovirus-using-microrna-targeting-strategy
#19
Mohammad Shayestehpour, Sharareh Moghim, Vahid Salimi, Somayeh Jalilvand, Jila Yavarian, Bizhan Romani, Talat Mokhtari-Azad
MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC)...
September 1, 2017: Virus Research
https://www.readbyqxmd.com/read/28796161/comparison-of-liver-detargeting-strategies-for-systemic-therapy-with-oncolytic-adenovirus-serotype-5
#20
Tien V Nguyen, Mary E Barry, Mallory A Turner, Catherine M Crosby, Miguel A Trujillo, John C Morris, Michael A Barry
Oncolytic viruses would ideally be of use for systemic therapy to treat disseminated cancer. To do this safely, this may require multiple layers of cancer specificity. The pharmacology and specificity of oncolytic adenoviruses can be modified by (1) physical retargeting, (2) physical detargeting, (3) chemical shielding, or (4) by modifying the ability of viral early gene products to selectively activate in cancer versus normal cells. We explored the utility of these approaches with oncolytic adenovirus serotype 5 (Ad5) in immunocompetent Syrian hamsters bearing subcutaneous HaK tumors...
August 10, 2017: Biomedicines
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