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Aid deaminase

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https://www.readbyqxmd.com/read/28490810/establishment-of-induced-pluripotent-stem-cells-from-normal-b-cells-and-inducing-aid-expression-in-their-differentiation-into-hematopoietic-progenitor-cells
#1
Fumihiko Kawamura, Makoto Inaki, Atsushi Katafuchi, Yu Abe, Naohiro Tsuyama, Yumiko Kurosu, Aki Yanagi, Mitsunori Higuchi, Satoshi Muto, Takumi Yamaura, Hiroyuki Suzuki, Hideyoshi Noji, Shinichi Suzuki, Mitsuaki A Yoshida, Megumi Sasatani, Kenji Kamiya, Masafumi Onodera, Akira Sakai
B cell derived induced pluripotent stem cells (BiPSCs) were recently established from peripheral blood B cells by the simultaneous transfection of Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPα using a Sendai virus vector. Here, using a different method, we established BiPSCs with immunoglobulin heavy chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The critical points of our method are pre-stimulation of B cells with IL-21 and CD40-ligand (CD40L), followed by consecutive transfection of highly concentrated Yamanaka factors using a retroviral vector...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479091/family-wide-comparative-analysis-of-cytidine-and-methylcytidine-deamination-by-eleven-human-apobec-proteins
#2
Fumiaki Ito, Yang Fu, Shen-Chi A Kao, Hanjing Yang, Xiaojiang S Chen
APOBECs are a family of cytidine deaminases involved in various important biological processes such as antibody diversification/maturation, restriction of viral infection, and generation of somatic mutations. Catalytically active APOBEC proteins execute their biological functions mostly through deaminating cytosine (C) to uracil on ssDNA/RNA. Activation-induced cytidine deaminase (AID), one of the APOBEC members, was reported to deaminate methylated cytosine (mC) on DNA and this mC deamination was proposed to be involved in demethylation of mC for epigenetic regulation...
May 4, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28472485/apobec3a-efficiently-deaminates-methylated-but-not-tet-oxidized-cytosine-bases-in-dna
#3
Emily K Schutsky, Christopher S Nabel, Amy K F Davis, Jamie E DeNizio, Rahul M Kohli
AID/APOBEC family enzymes are best known for deaminating cytosine bases to uracil in single-stranded DNA, with characteristic sequence preferences that can produce mutational signatures in targets such as retroviral and cancer cell genomes. These deaminases have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine (mC) or TET-oxidized mC bases (ox-mCs), which include 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. One specific family member, APOBEC3A (A3A), has been shown to readily deaminate mC, raising the prospect of broader activity on ox-mCs...
May 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28462376/regulation-of-gastric-metaplasia-dysplasia-and-neoplasia-by-bone-morphogenetic-protein-signaling
#4
REVIEW
Andrea Todisco
The bone morphogenetic proteins, (BMP)s are regulatory peptides that have significant effects on the growth and differentiation of gastrointestinal tissues. In addition, the BMPs have been shown to exert anti-inflammatory actions in the gut and to negatively regulate the growth of gastric neoplasms. The role of BMP signaling in the regulation of gastric metaplasia, dysplasia and neoplasia has been poorly characterized. Transgenic expression in the mouse stomach of the BMP inhibitor noggin leads to decreased parietal cell number, increased epithelial cell proliferation, and to the emergence of SPEM...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28461573/genetic-and-small-molecule-disruption-of-the-aid-rad51-axis-similarly-protects-nonobese-diabetic-mice-from-type-1-diabetes-through-expansion-of-regulatory-b-lymphocytes
#5
Jeremy J Ratiu, Jeremy J Racine, Muneer G Hasham, Qiming Wang, Jane A Branca, Harold D Chapman, Jing Zhu, Nina Donghia, Vivek Philip, William H Schott, Clive Wasserfall, Mark A Atkinson, Kevin D Mills, Caroline M Leeth, David V Serreze
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte-targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte-directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28445143/the-igh-locus-relocalizes-to-a-recombination-compartment-in-the-perinucleolar-region-of-differentiating-b-lymphocytes
#6
Andrey Pichugin, Olga V Iarovaia, Alexey Gavrilov, Ilya Sklyar, Natalja Barinova, Aleksandr Barinov, Evgeny Ivashkin, Gersende Caron, Said Aoufouchi, Sergey V Razin, Thierry Fest, Marc Lipinski, Yegor S Vassetzky
The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439266/a-novel-regulator-of-activation-induced-cytidine-deaminase-apobecs-in-immunity-and-cancer-schr%C3%A3-dinger-s-catalytic-pocket
#7
REVIEW
Justin J King, Mani Larijani
Activation-induced cytidine deaminase (AID) and its relative APOBEC3 cytidine deaminases boost immune response by mutating immune or viral genes. Because of their genome-mutating activities, AID/APOBECs are also drivers of tumorigenesis. Due to highly charged surfaces, extensive non-specific protein-protein/nucleic acid interactions, formation of polydisperse oligomers, and general insolubility, structure elucidation of these proteins by X-ray crystallography and NMR has been challenging. Hence, almost all available AID/APOBEC structures are of mutated and/or truncated versions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28429755/opossum-apobec1-is-a-dna-mutator-with-retrovirus-and-retroelement-restriction-activity
#8
Terumasa Ikeda, Mayuko Shimoda, Diako Ebrahimi, John L VandeBerg, Reuben S Harris, Atsushi Koito, Kazuhiko Maeda
APOBEC3s (A3s) are single-stranded DNA cytosine deaminases that provide innate immune defences against retroviruses and mobile elements. A3s are specific to eutherian mammals because no direct homologs exist at the syntenic genomic locus in metatherian (marsupial) or prototherian (monotreme) mammals. However, the A3s in these species have the likely evolutionary precursors, the antibody gene deaminase AID and the RNA/DNA editing enzyme APOBEC1 (A1). Here, we used cell culture-based assays to determine whether opossum A1 restricts the infectivity of retroviruses including human immunodeficiency virus type 1 (HIV-1) and the mobility of LTR/non-LTR retrotransposons...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28407558/cd11b-regulates-antibody-class-switching-via-induction-of-aid
#9
Seohyun Park, Hyunsub Sim, Hye-In Kim, Daecheol Jeong, Guang Wu, Soo Young Cho, Young Seek Lee, Hyung-Joo Kwon, Keunwook Lee
The integrin CD11b, which is encoded by the integrin subunit alpha M (ITGAM), is primarily expressed on the surface of innate immune cells. Genetic variations in ITGAM are among the strongest risk factors for systemic lupus erythematosus, an autoimmune disease characterized by the presence of autoantibodies. However, the regulatory function of CD11b in the antibody responses remains unclear. Here, we report the induction of CD11b in activated B2 B cells and define its unexpected role in immunoglobulin heavy chain class switch recombination (CSR)...
April 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28405512/high-expression-of-pd-1-ligands-is-associated-with-kataegis-mutational-signature-and-apobec3-alterations
#10
Amélie Boichard, Igor F Tsigelny, Razelle Kurzrock
Immunotherapy with checkpoint inhibitors, such as antibodies blocking the programmed cell-death receptor-1 (PD-1), has resulted in remarkable responses in patients having traditionally refractory cancers. Although response to PD-1 inhibitors correlates with PD-1 ligand (PD-L1 or PD-L2) expression, PD-1 ligand positivity represents only a part of the predictive model necessary for selecting patients predisposed to respond to immunotherapy. We used all genomic, transcriptomic, proteomic and phenotypic data related to 8,475 pan-cancer samples available in The Cancer Genome Atlas (TCGA) and conducted a logistic regression analysis based on a large set of variables, such as microsatellite instability (MSI-H), mismatch repair (MMR) alterations, polymerase δ (POLD1) and polymerase ε (POLE) mutations, activation-induced/apolipoprotein-B editing cytidine deaminases (AID/APOBEC) alterations, lymphocyte markers and mutation burden estimates to determine independent factors that associate with PD-1 ligand overexpression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28388279/investigation-of-aid-dicer-and-drosha-expressions-in-patients-with-chronic-lymphocytic-leukemia
#11
Metin Yusuf Gelmez, Ender Coskunpinar, Basak Saracoglu, Gunnur Deniz, Melih Aktan
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. Cytogenetic lesions such as del13q14, del11q22.3, and del17p13 are identified in 50-60% of patients. Activation-induced cytidine deaminase (AID) plays a central role in somatic hyper mutation (SHM) and class switch recombination (CSR) and functions on Ig genes, but also target non-Ig genes, and over-expression of AID can lead to point mutations or translocations in non-Ig genes such as IgH/Myc translocation. Dicer and Drosha, which have a role in activation process of miRNA, also act in a double-strand DNA break (DSB) repair mechanism...
April 7, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28381554/dna-mutagenic-activity-and-capacity-for-hiv-1-restriction-of-the-cytidine-deaminase-apobec3g-depends-on-whether-dna-or-rna-binds-to-tyrosine-315
#12
Bogdan Polevoda, Rebecca Joseph, Alan E Friedman, Ryan P Bennett, Rebecca Greiner, Thareendra De Zoysa, Ryan A Stewart, Harold C Smith
APOBEC3G (A3G) belongs to the AID/APOBEC protein family of cytidine deaminases (CDA) that bind to nucleic acids. A3G mutates the HIV genome by deamination of dC to dU, leading to accumulation of virus-inactivating mutations. Binding to cellular RNAs inhibits A3G binding to substrate single-stranded (ss) DNA and CDA activity. RNA and ssDNA bind to the same three A3G tryptic peptides (amino acids 181-194, 314-320, and 345-374) that form parts of a continuously exposed protein surface extending from the catalytic domain in the C-terminus of A3G to its N-terminus...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28362825/the-preferred-nucleotide-contexts-of-the-aid-apobec-cytidine-deaminases-have-differential-effects-when-mutating-retrotransposon-and-virus-sequences-compared-to-host-genes
#13
Jeffrey Chen, Thomas MacCarthy
The AID / APOBEC genes are a family of cytidine deaminases that have evolved in vertebrates, and particularly mammals, to mutate RNA and DNA at distinct preferred nucleotide contexts (or "hotspots") on foreign genomes such as viruses and retrotransposons. These enzymes play a pivotal role in intrinsic immunity defense mechanisms, often deleteriously mutating invading retroviruses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity maturation. We investigate the strength of various hotspots on their known biological targets by evaluating the potential impact of mutations on the DNA coding sequences of these targets, and compare these results to hypothetical hotspots that did not evolve...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28346401/targeted-base-editing-in-rice-and-tomato-using-a-crispr-cas9-cytidine-deaminase-fusion
#14
Zenpei Shimatani, Sachiko Kashojiya, Mariko Takayama, Rie Terada, Takayuki Arazoe, Hisaki Ishii, Hiroshi Teramura, Tsuyoshi Yamamoto, Hiroki Komatsu, Kenji Miura, Hiroshi Ezura, Keiji Nishida, Tohru Ariizumi, Akihiko Kondo
We applied a fusion of CRISPR-Cas9 and activation-induced cytidine deaminase (Target-AID) for point mutagenesis at genomic regions specified by single guide RNAs (sgRNAs) in two crop plants. In rice, we induced multiple herbicide-resistance point mutations by multiplexed editing using herbicide selection, while in tomato we generated marker-free plants with homozygous heritable DNA substitutions, demonstrating the feasibility of base editing for crop improvement.
May 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28333576/epstein-barr-virus-lytic-reactivation-activates-b-cells-polyclonally-and-induces-activation-induced-cytidine-deaminase-expression-a-mechanism-underlying-autoimmunity-and-its-contribution-to-graves-disease
#15
Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Hirotsugu Sugihara, Sayuri Hara, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Kazuhiko Hayashi
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity...
April 2017: Viral Immunology
https://www.readbyqxmd.com/read/28301039/bach2-regulates-aid-mediated-immunoglobulin-gene-conversion-and-somatic-hypermutation-in-dt40-b-cells
#16
Paulina M Budzyńska, Minna K Kyläniemi, Teemu Kallonen, Anni I Soikkeli, Kalle-Pekka Nera, Olli Lassila, Jukka Alinikula
The transcription factor Bach2 is required for germinal centre formation, somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28235482/srsf1-3-contributes-to-diversification-of-the-immunoglobulin-variable-region-gene-by-promoting-accumulation-of-aid-in-the-nucleus
#17
Yuka Kawaguchi, Hiroaki Nariki, Naoko Kawamoto, Yuichi Kanehiro, Satoshi Miyazaki, Mari Suzuki, Masaki Magari, Hiroshi Tokumitsu, Naoki Kanayama
Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28230119/editing-and-methylation-at-a-single-site-by-functionally-interdependent-activities
#18
Mary Anne T Rubio, Kirk W Gaston, Katherine M McKenney, Ian M C Fleming, Zdeněk Paris, Patrick A Limbach, Juan D Alfonzo
Nucleic acids undergo naturally occurring chemical modifications. Over 100 different modifications have been described and every position in the purine and pyrimidine bases can be modified; often the sugar is also modified. Despite recent progress, the mechanism for the biosynthesis of most modifications is not fully understood, owing, in part, to the difficulty associated with reconstituting enzyme activity in vitro. Whereas some modifications can be efficiently formed with purified components, others may require more intricate pathways...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28215280/molecular-mechanisms-of-somatic-hypermutation-and-class-switch-recombination
#19
S P Methot, J M Di Noia
In order to promote an efficient humoral immune response, germinal center B cells modify both the antigen recognition and effector domains by programmed genetic alterations of their antibody genes. To do so, B cells use the enzyme activation-induced deaminase (AID), which transforms deoxycytidine into deoxyuridine at the immunoglobulin genes, triggering mutagenic DNA repair. Data accumulated during the past decade have significantly advanced our understanding of how AID activity is regulated and preferentially targeted to the immunoglobulin genes...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28199836/bcr-and-endosomal-tlr-signals-synergize-to-increase-aid-expression-and-establish-central-b-cell-tolerance
#20
Masayuki Kuraoka, Pilar B Snowden, Takuya Nojima, Laurent Verkoczy, Barton F Haynes, Daisuke Kitamura, Garnett Kelsoe
Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell antigen receptor (BCR) and endosomal Toll-like receptor (TLR) signals synergize to elicit high levels of AID expression in immature/T1 B cells. This synergy is restricted to ligands for endocytic TLR and requires phospholipase-D activation, endosomal acidification, and MyD88...
February 14, 2017: Cell Reports
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