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Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia

M. Bellon, L. Lu, C. Nicot
2016 Blood  
Finally, preclinical testing of AZD1208 in a mouse model of ATL resulted in significant prevention of tumor growth in vivo.  ...  Our results revealed that STAT3, a direct target of miR-124a, is constitutively activated in HTLV-I-transformed cells and ATL cells, and activating STAT3 mutations were detected in 25.5% of primary ATL  ...  ATL-like cell lines ATL-T, ATL-25, ATL43T, ATL55T, KOB, KK1, and LM-Y1 were provided  ... 
doi:10.1182/blood-2015-11-685032 pmid:26813676 pmcid:PMC4874225 fatcat:e6i2zychkndubcixaf63mpia6u

Evolution of mutation rate and virulence among human retroviruses

Paul W. Ewald
1994 Philosophical Transactions of the Royal Society of London. Biological Sciences  
Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection.  ...  High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery.  ...  Given that genome size, nucleotide type and other unidentified factors will probably have an effect on mutation rates, I expect that the strongest tests of the general hypothesis will come from studies  ... 
doi:10.1098/rstb.1994.0150 pmid:7708828 fatcat:c5t2ggxda5cmti5vqj3ufyw6la

Membrane tethering by the atlastin GTPase depends on GTP hydrolysis but not on forming the cross-over configuration

Simran G. Saini, Chuang Liu, Peijun Zhang, Tina H. Lee, Benjamin S. Glick
2014 Molecular Biology of the Cell  
In this study, we used membrane-anchored atlastins in assays that separate tethering from fusion to dissect the requirements for each.  ...  Trans dimerization between atlastins anchored in opposing membranes, accompanied by a cross-over conformational change, is thought to draw the membranes together for fusion.  ...  Consequently we needed to confirm the effect of the corresponding mutations on D-ATL cross-over.  ... 
doi:10.1091/mbc.e14-08-1284 pmid:25253720 pmcid:PMC4244202 fatcat:4ory3o6hhvbudkqmbupyi7aogq

Loss of FBXW7-mediated degradation of BRAF elicits resistance to BET inhibitors in adult T cell leukemia cells

Chien-Hung Yeh, Marcia Bellon, Fang Wang, Hong Zhang, Liwu Fu, Christophe Nicot
2020 Molecular Cancer  
TET-inducible ATL cells carrying wild type or mutated FBXW7 were analyzed for target degradation and for drug sensitivity.  ...  Present treatment options are limited and there is no curative therapy for ATL. Ubiquitin ligase FBXW7 is commonly mutated or functionally inactivated in human cancers.  ...  The effects of JQ1 and OTX-015 were tested on MT1 cells carrying FBXW7 wild type or S462P mutant over a period of 16 days.  ... 
doi:10.1186/s12943-020-01254-x pmid:32907612 fatcat:gtvb6ypmbrcsbbu2gz73hfhbyy

Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion

T. Y. Liu, X. Bian, S. Sun, X. Hu, R. W. Klemm, W. A. Prinz, T. A. Rapoport, J. Hu
2012 Proceedings of the National Academy of Sciences of the United States of America  
S12 for the effect of all mutations tested).  ...  To dissect the function of the amphipathic helix, we tested the effect of point mutations on ATL-mediated membrane fusion.  ... 
doi:10.1073/pnas.1208385109 pmid:22802620 pmcid:PMC3420179 fatcat:2qvmrzma75czhbj5pujkdxheti

Modulating Activity of Vancomycin and Daptomycin on the Expression of Autolysis Cell-Wall Turnover and Membrane Charge Genes in hVISA and VISA Strains

Viviana Cafiso, Taschia Bertuccio, Daniela Spina, Simona Purrello, Floriana Campanile, Cinzia Di Pietro, Michele Purrello, Stefania Stefani, Sarah K. Highlander
2012 PLoS ONE  
. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality.  ...  Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin  ...  Acknowledgments We are grateful to Antony Bridgewood for the language revision and Dr. Marco Oggioni for his support in the statistical analysis of the results.  ... 
doi:10.1371/journal.pone.0029573 pmid:22253738 pmcid:PMC3253798 fatcat:whzi7vko3vhk5dbtsw6r7zxifq

Adult T-cell leukemia/lymphoma—pathobiology and implications for modern clinical management

Lucy Cook, Aileen Rowan, Charles Bangham
2021 Annals of Lymphoma  
Early detection of such mutations by targeted capture sequencing may enable more effective prevention of ATL by intervening at a time when the disease may be susceptible to therapies.  ...  Integration occurs throughout the human genome: it is not random but is biased toward transcriptionally active regions and near certain transcription factor binding sites, including those for STAT1, TP53  ... 
doi:10.21037/aol-21-6 fatcat:htamxfc2mjhihd5mqoivyriqyu

Flipping of alkylated DNA damage bridges base and nucleotide excision repair

Julie L. Tubbs, Vitaly Latypov, Sreenivas Kanugula, Amna Butt, Manana Melikishvili, Rolf Kraehenbuehl, Oliver Fleck, Andrew Marriott, Amanda J. Watson, Barbara Verbeek, Gail McGown, Mary Thorncroft (+10 others)
2009 Nature  
This effect is not due to decreased cell survival, as all mutants tested here are viable ( Supplementary Fig. 3 ).  ...  However, lack of structures, persuasive evidence, or specific mechanism has obscured how ATL ameliorates DNA damage effects.  ... 
doi:10.1038/nature08076 pmid:19516334 pmcid:PMC2729916 fatcat:g6uuyiqylffdvbev2gy4vfbcjy

IL-10-mediated signals act as a switch for lymphoproliferation in Human T-cell leukemia virus type-1 infection by activating the STAT3 and IRF4 pathways

Leila Sawada, Yoshiko Nagano, Atsuhiko Hasegawa, Hikari Kanai, Kai Nogami, Sayaka Ito, Tomoo Sato, Yoshihisa Yamano, Yuetsu Tanaka, Takao Masuda, Mari Kannagi, Susan R. Ross
2017 PLoS Pathogens  
potentially act as a switch for proliferation in HTLV-1-infected cells.  ...  may play a critical role in pushing HTLV-1-infected cells towards proliferation at the early stages of PLOS Pathogens | https://doi.  ...  Atae Utsunomiya (Imamura Bun-in Hospital, Kagoshima) for providing clinical samples and valuable advice, and S. Win from Edanz Group for editing a draft of this manuscript.  ... 
doi:10.1371/journal.ppat.1006597 pmid:28910419 pmcid:PMC5614654 fatcat:jdrtyg36tfhinn74nuczaohnee

Contribution of the Staphylococcus aureus Atl AM and GL Murein Hydrolase Activities in Cell Division, Autolysis, and Biofilm Formation

Jeffrey L. Bose, McKenzie K. Lehman, Paul D. Fey, Kenneth W. Bayles, Hung Ton-That
2012 PLoS ONE  
Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development  ...  Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm.  ...  In addition, we would like to thank Kari Nelson for aid in preparation of this manuscript.  ... 
doi:10.1371/journal.pone.0042244 pmid:22860095 pmcid:PMC3409170 fatcat:cpkbai3rpzfltcednpgvgjitnu

NOTCH1 Activation Depletes the Pool of Side Population Stem Cells in ATL

2017 Journal of Cancer Sciences  
maintenance of the SP cells in ATL.  ...  Methods-We isolated, sorted and characterized SP cells from uncultured PBMCs from ATL patients and from ATL patient-derived cell lines.  ...  The authors thank Brandi Miller for  ... 
doi:10.13188/2377-9292.1000013 pmid:28920078 pmcid:PMC5596512 fatcat:oqeqekk6cfcjfhtg4grfvcunhm

An activating mutation of interferon regulatory factor 4 (IRF4) in adult T-cell leukemia

Mathew A. Cherian, Sydney Olson, Hemalatha Sundaramoorthi, Kitra Cates, Xiaogang Cheng, John Harding, Andrew Martens, Grant A. Challen, Manoj Tyagi, Lee Ratner, Daniel Rauch
2018 Journal of Biological Chemistry  
IRF4 may represent a therapeutic target in ATL because ATL cells select for a mutant of IRF4 with higher nuclear expression and transcriptional activity, and overexpression of IRF4 induces the expansion  ...  We found that IRF4, which is transcriptionally activated downstream of these pathways, is frequently mutated in ATL.  ...  When we tested the effect of IRF4 on this promoter element, we saw strong induction, which would fully account for the high level of induction of the interferon ␤ promoter by IRF4.  ... 
doi:10.1074/jbc.ra117.000164 pmid:29540473 fatcat:vb4srvhdprgphk5rxvjq4tkwbm

Resistance Evolution Against Antimicrobial Peptides in Staphylococcus aureus Alters Pharmacodynamics Beyond the MIC

Baydaa El Shazely, Guozhi Yu, Paul R. Johnston, Jens Rolff
2020 Frontiers in Microbiology  
Except for one genotype, strains harboring mutations in menF and atl, all mutants had higher kappa than the non-selected sensitive controls.  ...  Although pharmacodynamics of antibiotic resistant strains have been studied, such data are lacking for AMP resistant strains.  ...  Petri for support, useful advices, and discussions.  ... 
doi:10.3389/fmicb.2020.00103 pmid:32117132 pmcid:PMC7033599 fatcat:dqsd5guw3jfanb2fzu2zorbq7u

Adult T-Cell Leukemia/Lymphoma (ATL): Pathogenesis, Treatment and Prognosis [chapter]

Shoko Kobayashi, Shigeki Iwasaki
2013 Clinical Epidemiology of Acute Lymphoblastic Leukemia - From the Molecules to the Clinic  
From these results, Gv-ATL effects played an important role in the outcome of allo-HSCT for ATL. [63] .  ...  The effect has to last for at least 1 month.  ... 
doi:10.5772/54776 fatcat:lem726dp6vc7hbkbifuda7a32a

Targeting General Transcriptional Machinery as a Therapeutic Strategy for Adult T-Cell Leukemia

Regina Wong, Takashi Ishida, Takaomi Sanda
2018 Molecules  
This approach would be particularly useful for genetically complicated cancers, such as adult T-cell leukemia (ATL), whereby a large mutational burden is present, but the functional consequences of each  ...  mutation have not been well-studied.  ...  Acknowledgments: We thank Phuong Cao Thi Ngoc for processing the ChIP-seq dataset in our previous study, and Stella Amanda and Wei Zhong Leong for their discussions and critical reviews.  ... 
doi:10.3390/molecules23051057 pmid:29724031 fatcat:degpvfzxxzdcrjvjzddnlakvg4
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