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Caiyang Liu, Huijie Cui, Dongqing Gu, Min Zhang, Yanfei Fang, Siyu Chen, Mingshuang Tang, Ben Zhang, Huanwen Chen
A growing number of studies investigating the association between Single Nucleotide Polymorphisms (SNPs) and lung cancer risk have been published since over a decade ago. An updated integrative assessment on the credibility and strength of the associations is required. We searched PubMed, Medline, and Web of Science on or before August 29(th), 2016. A total of 198 articles were deemed eligible for inclusion, which addressed the associations between 108 variants and lung cancer. Among the 108 variants, 63 were reported to be significantly associated with lung cancer while the remaining 45 were reported non-significant...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Kyle G Rodino, Lauren VieBrock, Sean M Evans, Hong Ge, Allen L Richards, Jason A Carlyon
Orientia tsutsugamushi, an obligate intracellular bacterium that is auxotrophic for the aromatic amino acids and histidine, causes scrub typhus, a potentially deadly infection that threatens one billion people. O. tsutsugamushi growth is minimal during the first 24 to 48 h of infection, but becomes logarithmic thereafter. How the pathogen modulates cellular functions to support its growth is poorly understood. The unfolded protein response (UPR) is a cytoprotective pathway that relieves endoplasmic reticulum (ER) stress by promoting ER-associated degradation (ERAD) of misfolded proteins...
November 6, 2017: Infection and Immunity
Juliane Daßler-Plenker, Katrin S Reiners, Jasper G van den Boorn, Hinrich P Hansen, Bastian Putschli, Sabine Barnert, Christine Schuberth-Wagner, Rolf Schubert, Thomas Tüting, Michael Hallek, Martin Schlee, Gunther Hartmann, Elke Pogge von Strandmann, Christoph Coch
Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I) by its specific ligand 5'-triphosphate-RNA (3pRNA) triggers antitumor immunity predominantly via NK cell activation and direct apoptosis induction in tumor cells. However, how NK cells are mobilized to attack the tumor cells remains elusive. Here, we show that RIG-I activation induced the secretion of extracellular vesicles (EVs) from melanoma cells, which by themselves revealed antitumor activity in vitro and in vivo. RIG-I-induced EVs from melanoma cells exhibited an increased expression of the NKp30-ligand (BAG6, BAT3) on their surface triggering NK cell-mediated lysis of melanoma cells via activation of the cytotoxicity NK cell-receptor NKp30...
2016: Oncoimmunology
Yeojin Lee, In Young Lee, Hee Jae Yun, Woo Sang Lee, Seongman Kang, Ssang-Goo Cho, Ji Eun Lee, Eui-Ju Choi
TNF receptor-associated factor 6 (TRAF6) plays a critical role in NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, both of which mediate macrophage activation in response to pathogen-associated molecular patterns such as bacterial endotoxin, lipopolysaccharides (LPS). In this study, we investigated whether HLA-B associated transcript-3 (BAT3) regulates LPS-induced macrophage activation. BAT3 physically interacted with TRAF6 in macrophages, and this interaction was enhanced in the cells after LPS treatment...
September 16, 2016: Biochemical and Biophysical Research Communications
Shotaro Saita, Takaya Ishihara, Maki Maeda, Shun-Ichiro Iemura, Tohru Natsume, Katsuyoshi Mihara, Naotada Ishihara
Mitochondrial morphology is dynamically regulated by fusion and fission. Several GTPase proteins control fusion and fission, and posttranslational modifications of these proteins are important for the regulation. However, it has not been clarified how the fusion and fission is balanced. Here, we report the molecular mechanism to regulate mitochondrial morphology in mammalian cells. Ablation of the mitochondrial fission, by repression of Drp1 or Mff, or by over-expression of MiD49 or MiD51, results in a reduction in the fusion GTPase mitofusins (Mfn1 and Mfn2) in outer membrane and long form of OPA1 (L-OPA1) in inner membrane...
May 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Xianying A Cui, Hui Zhang, Lena Ilan, Ai Xin Liu, Iryna Kharchuk, Alexander F Palazzo
Although one pathway for the post-translational targeting of tail-anchored proteins to the endoplasmic reticulum (ER) has been well defined, it is unclear whether additional pathways exist. Here, we provide evidence that a subset of mRNAs encoding tail-anchored proteins, including Sec61β and nesprin-2, is partially localized to the surface of the ER in mammalian cells. In particular, Sec61b mRNA can be targeted to, and later maintained on, the ER using both translation-dependent and -independent mechanisms...
September 15, 2015: Journal of Cell Science
Anne-Sophie Bach, Danielle Derocq, Valérie Laurent-Matha, Philippe Montcourrier, Salwa Sebti, Béatrice Orsetti, Charles Theillet, Céline Gongora, Sophie Pattingre, Eva Ibing, Pascal Roger, Laetitia K Linares, Thomas Reinheckel, Guillaume Meurice, Frank J Kaiser, Christian Gespach, Emmanuelle Liaudet-Coopman
The lysosomal protease cathepsin D (Cath-D) is overproduced in breast cancer cells (BCC) and supports tumor growth and metastasis formation. Here, we describe the mechanism whereby Cath-D is accumulated in the nucleus of ERα-positive (ER+) BCC. We identified TRPS1 (tricho-rhino-phalangeal-syndrome 1), a repressor of GATA-mediated transcription, and BAT3 (Scythe/BAG6), a nucleo-cytoplasmic shuttling chaperone protein, as new Cath-D-interacting nuclear proteins. Cath-D binds to BAT3 in ER+ BCC and they partially co-localize at the surface of lysosomes and in the nucleus...
September 29, 2015: Oncotarget
Nathan C Horton, Porunelloor A Mathew
Natural killer (NK) cells are a key constituent of the innate immune system, protecting against bacteria, virally infected cells, and cancer. Recognition and protective function against such cells are dictated by activating and inhibitory receptors on the surface of the NK cell, which bind to specific ligands on the surface of target cells. Among the activating receptors is a small class of specialized receptors termed the natural cytotoxicity receptors (NCRs) comprised of NKp30, NKp46, and NKp44. The NCRs are key receptors in the recognition and termination of virally infected and tumor cells...
2015: Frontiers in Immunology
Anna-Maria Katsori, Ajay Palagani, Nadia Bougarne, Dimitra Hadjipavlou-Litina, Guy Haegeman, Wim Vanden Berghe
In this study a series of curcumin analogues were evaluated for their ability to inhibit the activation of NF-κΒ, a transcription factor at the crossroads of cancer-inflammation. Our novel curcumin analogue BAT3 was identified to be the most potent NF-κB inhibitor and EMSA assays clearly showed inhibition of NF-κB/DNA-binding in the presence of BAT3, in agreement with reporter gene results. Immunofluorescence experiments demonstrated that BAT3 did not seem to prevent nuclear p65 translocation, so our novel analogue may interfere with NF-κB/DNA-binding or transactivation, independently of IKK2 regulation and NF-κB-translocation...
2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Paola Castillo, Abraham F Cetina, Alfonso Méndez-Tenorio, Lennane Michel Espinoza-Fonseca, Blanca L Barrón
BACKGROUND: Papillomavirus binding factor (PBF) or zinc finger protein 395 is a transcription factor associated to a poor prognosis in patients with osteosarcoma, an aggressive bone cancer that predominantly affects adolescents. To investigate the role of the PBF protein in the osteosarcoma genesis, in this paper we present the bioinformatics analysis of physicochemical properties of PBF and its probable interactions with several key cellular targets. RESULTS: The physicochemical characteristics determined to PBF, disorder-promoting amino acids, flexibility, hydrophobicity, prediction of secondary and tertiary structures and probability to be crystallized, supported that this protein can be considered as an intrinsically disordered protein (IDP), with a zinc finger-like domain...
2014: Theoretical Biology & Medical Modelling
Ignazio Stefano Piras, Andrea Angius, Marco Andreani, Manuela Testi, Guido Lucarelli, Matteo Floris, Sarah Marktel, Fabio Ciceri, Giorgio La Nasa, Katharina Fleischhauer, Maria Grazia Roncarolo, Alessandro Bulfone, Silvia Gregori, Rosa Bacchetta
The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants-other than HLA class I and II-associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R(2)=0...
November 2014: Bone Marrow Transplantation
Marina Saresella, Federica Piancone, Ivana Marventano, Francesca La Rosa, Paola Tortorella, Domenico Caputo, Marco Rovaris, Mario Clerici
T-cell immunoglobulin and mucin domain 3 (Tim-3) ligates galectin-9 (Gal-9); this process, resulting in the inhibition of Th1 responses and in the apoptosis of antigen-specific cells, is hampered by binding of the molecular adaptor human leukocyte antigen B (HLA-B)-associated transcript 3 (Bat3) to the intracellular tail of Tim-3. Apoptosis of myelin basic protein (MBP)-specific T lymphocytes correlates with reduced rates of disease progression in multiple sclerosis (MS). We extensively analyzed the Tim-3/Gal-9/Bat3 pathway in 87 patients with a diagnosis of stable relapsing-remitting MS (RRMS), primary progressive MS (PPMS), or benign MS (BEMS), as well as in 40 healthy control (HC) subjects...
November 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jiquan Chen, Yuan-Sheng Zang, Qingyu Xiu
Several studies have examined the associations of polymorphisms in HLA-B-associated transcript 3 (BAT3) with lung cancer risk. However, the results were conflicting. Thus, a meta-analysis was conducted to determine the relationship between BAT3 polymorphisms and lung cancer risk. Databases including PubMed, EMBASE, and Wanfang were searched. Summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated using random effects models or fixed effects models. Nine studies were included in this meta-analysis...
October 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Salwa Sebti, Christine Prébois, Esther Pérez-Gracia, Chantal Bauvy, Fabienne Desmots, Nelly Pirot, Céline Gongora, Anne-Sophie Bach, Andrew V Hubberstey, Valérie Palissot, Guy Berchem, Patrice Codogno, Laetitia K Linares, Emmanuelle Liaudet-Coopman, Sophie Pattingre
We recently reported that BAG6/BAT3 (BCL2-associated athanogene 6) is essential for basal and starvation-induced autophagy in E18.5 bag6(-/-) mouse embryos and in mouse embryonic fibroblasts (MEFs) through the modulation of the EP300/p300-dependent acetylation of TRP53 and autophagy-related (ATG) proteins. We observed that BAG6 increases TRP53 acetylation during starvation and pro-autophagic TRP53-target gene expression. BAG6 also decreases the EP300 dependent-acetylation of ATG5, ATG7, and LC3-I, posttranslational modifications that inhibit autophagy...
July 2014: Autophagy
Zhi-Qi Song, Li-Feng Yang, Yun-Sheng Wang, Ting Zhu, Xiang-Mei Zhou, Xiao-Min Yin, Hong-Qiang Yao, De-Ming Zhao
BACKGROUNDS AND AIMS: Prion diseases are a group of infectious neurodegenerative diseases characterized by neuronal death and degeneration. Human leukocyte antigen-B-associated transcript 3 (BAT3) is an important apoptosis regulator. We therefore investigated the interactions between BAT3 and prion protein and the potential role of BAT3 in PrP106-126-induced apoptosis. METHODS: BAT3 and prion protein were overexpressed in Hela, Neuro2A, or primary neuronal cells by transfection with BAT3-HA or PRNP-EGFP expression plasmids and their relationship studied by immunofluorescence and Western blotting...
August 2014: CNS Neuroscience & Therapeutics
Salwa Sebti, Christine Prébois, Esther Pérez-Gracia, Chantal Bauvy, Fabienne Desmots, Nelly Pirot, Céline Gongora, Anne-Sophie Bach, Andrew V Hubberstey, Valérie Palissot, Guy Berchem, Patrice Codogno, Laetitia K Linares, Emmanuelle Liaudet-Coopman, Sophie Pattingre
Autophagy is regulated by posttranslational modifications, including acetylation. Here we show that HLA-B-associated transcript 3 (BAT3) is essential for basal and starvation-induced autophagy in embryonic day 18.5 BAT3(-/-) mouse embryos and in mouse embryonic fibroblasts (MEFs) through the modulation of p300-dependent acetylation of p53 and ATG7. Specifically, BAT3 increases p53 acetylation and proautophagic p53 target gene expression, while limiting p300-dependent acetylation of ATG7, a mechanism known to inhibit autophagy...
March 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
Wei Wu, Qin-shan Li, Wei Song, Shi-ying Miao, Lin-fang Wang
OBJECTIVE: To identify the specific protein interactions involved in Bat3-mediated apoptosis. METHODS: Tandem affinity purification (TAP) was utilized to investigate Bat3-protein interactions, during which full-length human Bat3 fused with Strep2 and FLAG tag as a bait was used to screen the specific protein-protein interactions. The isolated proteins were identified with mass spectrometry. RESULTS: TAP studies showed that Ubl4A was identified as a Bat3-binding partner...
February 2014: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
Sylvia Hartmann, Claudia Döring, Christina Jakobus, Benjamin Rengstl, Sebastian Newrzela, Thomas Tousseyn, Xavier Sagaert, Maurilio Ponzoni, Fabio Facchetti, Chris de Wolf-Peeters, Christian Steidl, Randy Gascoyne, Ralf Küppers, Martin-Leo Hansmann
In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities...
2013: PloS One
Ian A Yang, John W Holloway, Kwun M Fong
Lung cancer is a leading cause of cancer death and disease burden in many countries. Understanding of the biological pathways involved in lung cancer aetiology is required to identify key biomolecules that could be of significant clinical value, either as predictive, prognostic or diagnostic markers, or as targets for the development of novel therapies to treat this disease, in addition to smoking avoidance strategies. Genome-wide association studies (GWAS) have enabled significant progress in the past 5 years in investigating genetic susceptibility to lung cancer...
October 2013: Journal of Thoracic Disease
Janina Binici, Jessica Hartmann, Julia Herrmann, Christine Schreiber, Steffen Beyer, Günnur Güler, Vitali Vogel, Franz Tumulka, Rupert Abele, Werner Mäntele, Joachim Koch
Immunosurveillance of tumor cells depends on NKp30, a major activating receptor of human natural killer (NK) cells. The human BCL2-associated athanogene 6 (BAG-6, also known as BAT3; 1126 amino acids) is a cellular ligand of NKp30. To date, little is known about the molecular details of this receptor ligand system. Within the current study, we have located the binding site of NKp30 to a sequence stretch of 250 amino acids in the C-terminal region of BAG-6 (BAG-6(686-936)). BAG-6(686-936) forms a noncovalent dimer of 57-59 kDa, which is sufficient for high affinity interaction with NKp30 (KD < 100 nM)...
November 29, 2013: Journal of Biological Chemistry
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