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Activation induced cytidine deaminase AID

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https://www.readbyqxmd.com/read/28790320/activation-induced-cytidine-deaminase-targets-suv4-20-mediated-histone-h4k20-trimethylation-to-class-switch-recombination-sites
#1
Virginia C Rodríguez-Cortez, Paloma Martínez-Redondo, Francesc Català-Moll, Javier Rodríguez-Ubreva, Antonio Garcia-Gomez, Ganesh Poorani-Subramani, Laura Ciudad, Henar Hernando, Arantxa Pérez-García, Carlos Company, José M Urquiza, Almudena R Ramiro, Javier M Di Noia, Alejandro Vaquero, Esteban Ballestar
Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757211/aid-recognizes-structured-dna-for-class-switch-recombination
#2
Qi Qiao, Li Wang, Fei-Long Meng, Joyce K Hwang, Frederick W Alt, Hao Wu
Activation-induced cytidine deaminase (AID) initiates both class switch recombination (CSR) and somatic hypermutation (SHM) in antibody diversification. Mechanisms of AID targeting and catalysis remain elusive despite its critical immunological roles and off-target effects in tumorigenesis. Here, we produced active human AID and revealed its preferred recognition and deamination of structured substrates. G-quadruplex (G4)-containing substrates mimicking the mammalian immunoglobulin switch regions are particularly good AID substrates in vitro...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28724724/brct-domain-protein-brit1-influences-class-switch-recombination
#3
Wei-Feng Yen, Ashutosh Chaudhry, Bharat Vaidyanathan, William T Yewdell, Joseph N Pucella, Rahul Sharma, Yulong Liang, Kaiyi Li, Alexander Y Rudensky, Jayanta Chaudhuri
DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range DNA end-joining while suppressing genomic instability inherently associated with DSBs are yet to be fully elucidated. Here, we use a targeted short-hairpin RNA screen in a B-cell lymphoma line to identify the BRCT-domain protein BRIT1 as an effector of CSR. We show that conditional genetic deletion of BRIT1 in mice leads to a marked increase in unrepaired Igh breaks and a significant reduction in CSR in ex vivo activated splenic B cells...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716949/biochemical-regulatory-features-of-aid-remain-conserved-from-lamprey-to-humans
#4
Emma M Quinlan, Justin J King, Chris T Amemiya, Ellen Hsu, Mani Larijani
Activation induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties of human AID and found that it is an unusual enzyme in that it exhibits binding affinities for its substrate DNA and catalytic rates several orders of magnitude higher and lower, respectively, than a typical enzyme. Recently, we solved the functional structure of AID and demonstrated that these properties are due to non-specific DNA binding on its surface, along with a catalytic pocket that predominantly assumes a closed conformation...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28707393/malaria-epstein-barr-virus-infection-and-the-pathogenesis-of-burkitt-s-lymphoma
#5
Anthony R Mawson, Suvankar Majumdar
A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR, Path Global Health 2013;107(3):122-9)...
July 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28693209/frequent-aberrant-p53-and-fhit-expression-in-endoscopically-resected-superficial-hypopharyngeal-cancer-and-esophageal-cancer
#6
Sohei Yamamoto, Kazuo Yashima, Soichiro Kawata, Kohei Hosoda, Akihiro Tamoto, Yuichiro Ikebuchi, Kazuya Matsumoto, Koichiro Kawaguchi, Kenichi Harada, Yoshikazu Murawaki, Hajime Isomoto
In the last decade, the incidence rate of detection rate of superficial head, neck and esophageal squamous cell carcinomas has increased with the development of endoscopic imaging techniques. These cancers are thought to arise independently subsequent to tissue exposure to a common carcinogen e.g. alcohol or tobacco. This phenomenon has been termed field cancerization. To determine the molecular background of the development of hypopharyngeal squamous cell carcinomas (HPSCCs) and double esophageal squamous cell carcinomas (DESCCs), the present study immunohistochemically assessed tumor-related protein expression [p53, Fhit (fragile histidine triad), E-cadherin and activation-induced cytidine deaminase (AID)], and subsequently determined the correlation between protein expression and clinicopathological data...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28676801/cd25-b-1a-cells-express-aicda
#7
Hiroaki Kaku, Nichol E Holodick, Joseph R Tumang, Thomas L Rothstein
B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID), a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO) mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC) B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634398/mutations-in-human-aid-differentially-affect-its-ability-to-deaminate-cytidine-and-5-methylcytidine-in-ssdna-substrates-in-vitro
#8
Lucyna Budzko, Paulina Jackowiak, Karol Kamel, Joanna Sarzynska, Janusz M Bujnicki, Marek Figlerowicz
Activation-induced cytidine deaminase (AID) is known for its established role in antibody production. AID induces the diversification of antibodies by deaminating deoxycytidine (C) within immunoglobulin genes. The capacity of AID to deaminate 5-methyldeoxycytidine (5 mC) and/or 5-hydroxymethyldeoxycytidine (5 hmC), and consequently AID involvement in active DNA demethylation, is not fully resolved. For instance, structural determinants of AID activity on different substrates remain to be identified. To better understand the latter issue, we tested how mutations in human AID (hAID) influence its ability to deaminate C, 5 mC, and 5 hmC in vitro...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630076/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-is-affinity-maturation-a-self-defeating-process-for-eliciting-broad-protection
#9
Christopher T Stamper, Patrick C Wilson
Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28626219/base-excision-repair-proteins-couple-activation-induced-cytidine-deaminase-and-endonuclease-g-during-replication-stress-induced-mll-destabilization
#10
B Gole, E Mian, M Rall, L Wiesmüller
The breakpoint cluster region of the MLL gene (MLLbcr) is frequently rearranged in therapy-related and infant acute leukaemia, but the destabilizing mechanism is poorly understood. We recently proposed that DNA replication stress results in MLLbcr cleavage via Endonuclease G (EndoG) and represents the common denominator of genotoxic therapy-induced MLL destabilization. Here we performed a siRNA screen for new factors involved in replication stress-induced MLL rearrangements employing an EGFP-based reporter system...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28621910/allospecific-memory-b-cell-responses-are-dependent-on-autophagy
#11
M Fribourg, J Ni, F Nina Papavasiliou, Z Yue, P S Heeger, J S Leventhal
Long-lived, donor-reactive memory B cells (Bmems) can produce alloantibodies that mediate transplant injury. Autophagy, an intrinsic mechanism of cell organelle/component recycling, is required for Bmem survival in infectious and model antigen systems, but whether autophagy affects alloreactive Bmem is unknown. We studied mice with an inducible yellow fluorescent protein (YFP) reporter expressed under the activation-induced cytidine deaminase (AID) promoter active in B cells undergoing germinal center reactions...
June 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28589361/the-aid-cre-ert2-model-a-tool-for-monitoring-b-cell-immune-responses-and-generating-selective-hybridomas
#12
Simon Le Gallou, Takuya Nojima, Daisuke Kitamura, Jean-Claude Weill, Claude-Agnès Reynaud
Expression of activation-induced cytidine deaminase (AID) is the hallmark of B cells engaged in an immune response in germinal centers. We designed an inducible fate-mapping reporter mouse in which AID-expressing B cells could be timely and irreversibly marked, by knockin at the Aicda locus of a tamoxifen-inducible Cre recombinase. This mouse model allows notably for the long-term follow-up of memory B cells and plasma cells engaged in an immune response. We describe here a protocol to generate hybridomas from small memory subsets that can be easily traced and identified in this mouse line through Cre-activated fluorescent reporters...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28588701/aberrant-expression-of-aid-and-aid-activators-of-nf-%C3%AE%C2%BAb-and-pax5-is-irrelevant-to-ebv-associated-gastric-cancers-but-is-associated-with-carcinogenesis-in-certain-ebv-non-associated-gastric-cancers
#13
Takashi Mohri, Keiko Nagata, Satoshi Kuwamoto, Michiko Matsushita, Hirotsugu Sugihara, Masako Kato, Yasushi Horie, Ichiro Murakami, Kazuhiko Hayashi
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric cancer characterized by clinicopathological features including lymphoepithelioma-like histology. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related nuclear factor κB (NF-κB) signaling in Helicobacter pylori-associated gastric cancer. To elucidate whether or not AID expression is relevant to carcinogenesis in EBVaGC, immunohistochemical expression of AID and AID-regulatory factors between EBVaGC and EBV-non-associated gastric carcinoma (GC) were evaluated, each using 15 cases of GC with lymphoid stroma (GCLS) and other types of GC...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28575114/early-derivation-of-igm-memory-cells-and-bone-marrow-plasmablasts
#14
Amber M Papillion, Kevin J Kenderes, Jennifer L Yates, Gary M Winslow
IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of these cells was unknown, although an early T-independent spleen CD11c- and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship. A majority of the IgM memory cells detected after day 30 post-infection, also T-bet-positive, had undergone somatic hypermutation, indicating they expressed activation-induced cytidine deaminase (AID)...
2017: PloS One
https://www.readbyqxmd.com/read/28544233/overexpression-of-b-cell-lymphoma-6-alters-gene-expression-profile-in-a-myeloma-cell-line-and-is-associated-with-decreased-dna-damage-response
#15
Kenichi Tahara, Makiko Takizawa, Arito Yamane, Yohei Osaki, Takuma Ishizaki, Takeki Mitsui, Akihiko Yokohama, Takayuki Saitoh, Norifumi Tsukamoto, Morio Matsumoto, Hirokazu Murakami, Yoshihisa Nojima, Hiroshi Handa
B-cell lymphoma 6 (BCL6) attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28541550/integrity-of-immunoglobulin-variable-region-is-supported-by-ganp-during-aid-induced-somatic-hypermutation-in-germinal-center-b-cells
#16
Mohammed Mansour Abbas Eid, Mayuko Shimoda, Shailendra Kumar Singh, Sarah Ameen Almofty, Phuong Pham, Myron F Goodman, Kazuhiko Maeda, Nobuo Sakaguchi
Immunoglobulin (Ig) affinity maturation depends on somatic hypermutation (SHM) in variable (V) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs create transversion mutations at C/G and mutations at A/T sites. In Neuberger's model, it remained to clarify how transition/transversion repair is regulated. We investigate role of AID-interacting GANP (germinal-center associated nuclear protein) in IgV SHM profile...
May 24, 2017: International Immunology
https://www.readbyqxmd.com/read/28535205/a-transcriptional-serenaid-the-role-of-noncoding-rnas-in-class-switch-recombination
#17
William T Yewdell, Jayanta Chaudhuri
During an immune response, activated B cells may undergo class switch recombination (CSR), a molecular rearrangement that allows B cells to switch from expressing IgM and IgD to a secondary antibody heavy chain isotype such as IgG, IgA, or IgE. Secondary antibody isotypes provide the adaptive immune system with distinct effector functions to optimally combat various pathogens. CSR occurs between repetitive DNA elements within the immunoglobulin heavy chain (Igh) locus, termed switch (S) regions, and requires the DNA modifying enzyme activation-induced cytidine deaminase (AID)...
May 23, 2017: International Immunology
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
#18
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
#19
Fumiaki Ito, Yang Fu, Shen-Chi A Kao, Hanjing Yang, Xiaojiang S Chen
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) proteins 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 single-stranded DNA/RNA. Activation-induced cytidine deaminase, one of the APOBEC members, was reported to deaminate methylated cytosine (mC) on DNA, and this mC deamination was proposed to be involved in the demethylation of mC for epigenetic regulation...
June 16, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28462376/regulation-of-gastric-metaplasia-dysplasia-and-neoplasia-by-bone-morphogenetic-protein-signaling
#20
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
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