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https://www.readbyqxmd.com/read/28323255/erratum-hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#1
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#2
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28190795/progress-in-understanding-the-molecular-functions-of-ddx3y-dby-in-male-germ-cell-development-and-maintenance
#3
Alexei A Kotov, Oxana M Olenkina, Baira K Godneeva, Vladimir E Adashev, Ludmila V Olenina
Human DDX3 paralogs are housed on the X chromosome (DDX3X) as well as in the non- recombining region Yq11 of the Y-chromosome (DDX3Y or DBY). A gene encoding RNA helicase DDX3Y is located in the AZoospermia Factor a (AZFa) region of the Y-chromosome and expressed only in male germ cells. Deletions encompassing the DDX3Y gene lead to azoospermia and cause Sertoli Cell-Only Syndrome (SCOS) in humans. SCOS is characterized by a complete germ cell lack with preservation of somatic Sertoli cells. This review summarizes current advances in the study of DDX3Y functions in maintenance and development of early male germ cells...
February 12, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28138868/combination-treatment-using-ddx3-and-parp-inhibitors-induces-synthetic-lethality-in-brca1-proficient-breast-cancer
#4
Marise R Heerma van Voss, Justin D Brilliant, Farhad Vesuna, Guus M Bol, Elsken van der Wall, Paul J van Diest, Venu Raman
Triple-negative breast cancers have unfavorable outcomes due to their inherent aggressive behavior and lack of targeted therapies. Breast cancers occurring in BRCA1 mutation carriers are mostly triple-negative and harbor homologous recombination deficiency, sensitizing them to inhibition of a second DNA damage repair pathway by, e.g., PARP inhibitors. Unfortunately, resistance against PARP inhibitors in BRCA1-deficient cancers is common and sensitivity is limited in BRCA1-proficient breast cancers. RK-33, an inhibitor of the RNA helicase DDX3, was previously demonstrated to impede non-homologous end-joining repair of DNA breaks...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28128295/rna-helicase-ddx3-maintains-lipid-homeostasis-through-upregulation-of-the-microsomal-triglyceride-transfer-protein-by-interacting-with-hnf4-and-shp
#5
Tsung-Yuan Tsai, Wei-Ting Wang, Hao-Kang Li, Wei-Ju Chen, Yu-Hong Tsai, Chi-Hong Chao, Yan-Hwa Wu Lee
Multifunctional RNA helicase DDX3 participates in HCV infection, one of the major causes of hepatic steatosis. Here, we investigated the role of DDX3 in hepatic lipid metabolism. We found that HCV infection severely reduced DDX3 expression. Analysis of intracellular triglyceride and secreted ApoB indicated that lipid accumulations were increased while ApoB secretion were decreased in DDX3 knockdown HuH7 and HepG2 cell lines. Down-regulation of DDX3 significantly decreased protein and transcript expression of microsomal triglyceride transfer protein (MTP), a key regulator of liver lipid homeostasis...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28030561/drosophila-ddx3-belle-exerts-its-function-outside-of-the-wnt-wingless-signaling-pathway
#6
Fabian H Jenny, Konrad Basler
The helicases human DDX3 and Drosophila Belle (Bel) are part of a well-defined subfamily of the DEAD-box helicases. Individual subfamily-members perform a myriad of functions in nuclear and cytosolic RNA metabolism. It has also been reported that DDX3X is involved in cell signaling, including IFN-α and IFN-β inducing pathways upon viral infection as well as in Wnt signaling. Here we used a collection of EMS-induced bel alleles recovered from a Wingless (Wg) suppressor screen to analyze the role of the Drosophila homolog of DDX3 in Wg/Wnt signaling...
2016: PloS One
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#7
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27999982/the-prognostic-effect-of-ddx3-upregulation-in-distant-breast-cancer-metastases
#8
Marise R Heerma van Voss, Willemijne A M E Schrijver, Natalie D Ter Hoeve, Laurien D Hoefnagel, Quirine F Manson, Elsken van der Wall, Venu Raman, Paul J van Diest
Metastatic breast cancer remains one of the leading causes of death in women and identification of novel treatment targets is therefore warranted. Functional studies showed that the RNA helicase DDX3 promotes metastasis, but DDX3 expression was never studied in patient samples of metastatic cancer. In order to validate previous functional studies and to evaluate DDX3 as a potential therapeutic target, we investigated DDX3 expression in paired samples of primary and metastatic breast cancer. Samples from 79 breast cancer patients with distant metastases at various anatomical sites were immunohistochemically stained for DDX3...
January 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/27980081/ddx3-directly-regulates-traf3-ubiquitination-and-acts-as-a-scaffold-to-coordinate-assembly-of-signalling-complexes-downstream-of-mavs
#9
Lili Gu, Anthony Fullam, Niamh McCormack, Yvette Hoehn, Martina Schroeder
Human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IκB-kinase-ε (IKKε), the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination...
December 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27736973/the-dead-box-rna-helicase-ddx3-interacts-with-nf-%C3%AE%C2%BAb-subunit-p65-and-suppresses-p65-mediated-transcription
#10
Nian Xiang, Miao He, Musarat Ishaq, Yu Gao, Feifei Song, Liang Guo, Li Ma, Guihong Sun, Dan Liu, Deyin Guo, Yu Chen
RNA helicase family members exhibit diverse cellular functions, including in transcription, pre-mRNA processing, RNA decay, ribosome biogenesis, RNA export and translation. The RNA helicase DEAD-box family member DDX3 has been characterized as a tumour-associated factor and a transcriptional co-activator/regulator. Here, we demonstrate that DDX3 interacts with the nuclear factor (NF)-κB subunit p65 and suppresses NF-κB (p65/p50)-mediated transcriptional activity. The downregulation of DDX3 by RNA interference induces the upregulation of NF-κB (p65/p50)-mediated transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27735940/ddx3-dead-box-rna-helicase-plays-a-central-role-in-mitochondrial-protein-quality-control-in-leishmania
#11
Prasad Kottayil Padmanabhan, Ouafa Zghidi-Abouzid, Mukesh Samant, Carole Dumas, Bruno Guedes Aguiar, Jerome Estaquier, Barbara Papadopoulou
DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27634756/rk-33-radiosensitizes-prostate-cancer-cells-by-blocking-the-rna-helicase-ddx3
#12
Min Xie, Farhad Vesuna, Saritha Tantravedi, Guus M Bol, Marise R Heerma van Voss, Katriana Nugent, Reem Malek, Kathleen Gabrielson, Paul J van Diest, Phuoc T Tran, Venu Raman
Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27572922/c-terminal-residues-specific-to-vasa-among-dead-box-helicases-are-required-for-its-functions-in-pirna-biogenesis-and-embryonic-patterning
#13
Mehrnoush Dehghani, Paul Lasko
The DEAD-box RNA helicase Vasa (Vas, also known as DDX4) is required for germ cell development. In Drosophila, analysis of hypomorphic mutations has implicated maternally expressed Vas in germ cell formation and posterior embryonic patterning. vas-null females, which rarely complete oogenesis, exhibit defects in mitotic progression of germline stem cells, Piwi-interacting RNA (piRNA)-mediated transposon silencing, and translation of Gurken (Grk), an EGFR ligand. The carboxy-terminal region of Vas orthologs throughout the animal kingdom consists of several acidic residues as well as an invariant tryptophan in the penultimate or ultimate position (Trp660 in Drosophila melanogaster)...
November 2016: Development Genes and Evolution
https://www.readbyqxmd.com/read/27344963/ddx3-represses-stemness-by-epigenetically-modulating-tumor-suppressive-mirnas-in-hepatocellular-carcinoma
#14
Hao-Kang Li, Ru-Tsun Mai, Hsien-Da Huang, Chih-Hung Chou, Yi-An Chang, Yao-Wen Chang, Li-Ru You, Chun-Ming Chen, Yan-Hwa Wu Lee
Studies indicate that the presence of cancer stem cells (CSCs) is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, the functional role of DDX3 in regulation of hepatic CSCs was investigated. Our results demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of HCC patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoreisistance, EMT, migration as well as CSC expansion, and most importantly, DDX3 knockdown promotes tumorigenesis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27300509/immunosuppressive-yersinia-effector-yopm-binds-dead-box-helicase-ddx3-to-control-ribosomal-s6-kinase-in-the-nucleus-of-host-cells
#15
Laura Berneking, Marie Schnapp, Andreas Rumm, Claudia Trasak, Klaus Ruckdeschel, Malik Alawi, Adam Grundhoff, Alexey G Kikhney, Friedrich Koch-Nolte, Friedrich Buck, Markus Perbandt, Christian Betzel, Dmitri I Svergun, Moritz Hentschke, Martin Aepfelbacher
Yersinia outer protein M (YopM) is a crucial immunosuppressive effector of the plaque agent Yersinia pestis and other pathogenic Yersinia species. YopM enters the nucleus of host cells but neither the mechanisms governing its nucleocytoplasmic shuttling nor its intranuclear activities are known. Here we identify the DEAD-box helicase 3 (DDX3) as a novel interaction partner of Y. enterocolitica YopM and present the three-dimensional structure of a YopM:DDX3 complex. Knockdown of DDX3 or inhibition of the exportin chromosomal maintenance 1 (CRM1) increased the nuclear level of YopM suggesting that YopM exploits DDX3 to exit the nucleus via the CRM1 export pathway...
June 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27252702/accessory-factors-of-cytoplasmic-viral-rna-sensors-required-for-antiviral-innate-immune-response
#16
REVIEW
Hiroyuki Oshiumi, Takahisa Kouwaki, Tsukasa Seya
Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27186411/multifunctional-ddx3-dual-roles-in-various-cancer-development-and-its-related-signaling-pathways
#17
REVIEW
Luqing Zhao, Yitao Mao, Jianhua Zhou, Yuelong Zhao, Ya Cao, Xiang Chen
DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box protein, which is a cluster of ATP-dependent and the largest family of RNA helicase. DEAD-box family is characterized by the regulation of ATPase and helicase activities, the modulation of RNA metabolism, and the actors of RNA binding proteins or molecular chaperones to interact with other proteins or RNA. For DDX3, it exerts its multifaceted roles in viral manipulation, stress response, hypoxia, radiation response and apoptosis, and is closely related to cancer development and progression...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27179789/targeted-inactivation-of-murine-ddx3x-essential-roles-of-ddx3x-in-placentation-and-embryogenesis
#18
Chia-Yu Chen, Chieh-Hsiang Chan, Chun-Ming Chen, Yin-Shuan Tsai, Tsung-Yuan Tsai, Yan-Hwa Wu Lee, Li-Ru You
The X-linked DEAD-box RNA helicase DDX3 (DDX3X) is a multifunctional protein that has been implicated in gene regulation, cell cycle control, apoptosis, and tumorigenesis. However, the precise physiological function of Ddx3x during development remains unknown. Here, we show that loss of Ddx3x results in an early post-implantation lethality in male mice. The size of the epiblast marked by Oct3/4 is dramatically reduced in embryonic day 6.5 (E6.5) Ddx3x(-)/Y embryos. Preferential paternal X chromosome inactivation (XCI) in extraembryonic tissues of Ddx3x heterozygous (Ddx3x(-/+)) female mice with a maternally inherited null allele leads to placental abnormalities and embryonic lethality during development...
May 14, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27118832/human-ddx3-protein-is-a-valuable-target-to-develop-broad-spectrum-antiviral-agents
#19
Annalaura Brai, Roberta Fazi, Cristina Tintori, Claudio Zamperini, Francesca Bugli, Maurizio Sanguinetti, Egidio Stigliano, José Esté, Roger Badia, Sandra Franco, Miguel A Martinez, Javier P Martinez, Andreas Meyerhans, Francesco Saladini, Maurizio Zazzi, Anna Garbelli, Giovanni Maga, Maurizio Botta
Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus...
May 10, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27105836/venezuelan-equine-encephalitis-virus-non-structural-protein-3-nsp3-interacts-with-rna-helicases-ddx1-and-ddx3-in-infected-cells
#20
Moushimi Amaya, Taryn Brooks-Faulconer, Tyler Lark, Forrest Keck, Charles Bailey, Venu Raman, Aarthi Narayanan
The mosquito-borne New World alphavirus, Venezuelan equine encephalitis virus (VEEV) is a Category B select agent with no approved vaccines or therapies to treat infected humans. Therefore it is imperative to identify novel targets that can be targeted for effective therapeutic intervention. We aimed to identify and validate interactions of VEEV nonstructural protein 3 (nsP3) with host proteins and determine the consequences of these interactions to viral multiplication. We used a HA tagged nsP3 infectious clone (rTC-83-nsP3-HA) to identify and validate two RNA helicases: DDX1 and DDX3 that interacted with VEEV-nsP3...
July 2016: Antiviral Research
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