The human cytidine deaminase Apobec3F (h-A3F) a protein linked to the previously recognized antiviral factor Apobec3G (h-A3G) has antiviral activity against individual immunodeficiency virus type 1 (HIV-1) thats suppressed with the viral protein Vif. E3 ubiquitin ligase. Disturbance with Cul5-E3 ligase function by depletion of Cul5 through RNA disturbance or overexpression of Cul5 mutants obstructed the power of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that didnt recruit Cul5-E3 ligase but was still in a position to connect to h-A3F didnt suppress h-A3F. Oddly enough disturbance with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also elevated the balance of HIV-1 Vif recommending that just like the substrate substances h-A3F and h-A3G the substrate receptor proteins Vif is certainly itself also governed by Cul5-E3 ligase. Our outcomes indicate that Cul5-E3 ligase is apparently a common pathway hijacked by HIV-1 Vif to beat both h-A3F and h-A3G. Developing ...
Quantitative RT-PCR analysis of activation-induced cytidine deaminase expression in tissue samples from mantle cell lymphoma and B-cell chronic lymphocytic leukemia patients ...
Source: NIH.gov. A set of proteins involved in the bodys natural defences produces a large number of mutations in human DNA, according to a study led by researchers at the National Institutes of Health. The findings suggest that these naturally produced mutations are just as powerful as known cancer-causing agents in producing tumors.. The proteins are part of a group called apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytidine deaminases. The investigators found that APOBEC mutations can outnumber all other mutations in some cancers, accounting for over two-thirds in some bladder, cervical, breast, head and neck, and lung tumours.. The scientists published their findings online July 14 in the journal Nature Genetics. Dmitry Gordenin, Ph.D., is corresponding author of the paper and a senior associate scientist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. He said scientists knew the main functions of APOBEC cytosine deaminases were ...
Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S areas, respectively, in activated B cells. in DT40 cells elevated the pace of AID-induced BMS-754807 gene conversion as much as 5-collapse. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion. Author Summary To generate highly specific antibodies in response to an immune challenge, the antibody genes in triggered B cells mutate at a very high rate over a period of several days. The enzyme that initiates antibody gene mutation is definitely activation-induced cytidine deaminase (AID), the 1st protein recognized to directly edit DNA genomes BMS-754807 in vivo. AID induces point mutation of antibody V genes in all vertebrates, as well as transfer ...
To investigate whether the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway participates in the regulation of APOBEC3G (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) gene transcription and to study the molecular mechanisms of interferon resistance in patients with chronic hepatitis B (CHB), changes in APOBEC3G and STAT-1 expression levels in HepG2.2.15 cells after treatment with various concentrations of IFN-a, were detected using real-time RT-PCR and Western-blot. In addition, the differences in STAT-1 and APOBEC3G expression in liver tissues were also observed in patients with different anti-viral responses to IFN-a. It is found that IFN-a suppressed HBV replication and expression markedly in HepG2.2.15 cells, and simultaneously enhanced APOBEC3G expression in a dose- or time-dependent manner within a certain range. Moreover, a corresponding gradual increase in STAT-1 expression levels was also observed. The expression levels of STAT-1 and
Activation-induced deaminase (AID) is expressed only in germinal center B cells. There, it is required for somatic hypermutation, gene conversion and class switch recombination of antibody variable region segments, three processes that diversify antibodies during immune responses. Although AID has homology to RNA-editing enzymes, three recent reports suggest it could initiate the diversification processes by deaminating cytidine residues within the antibody genes themselves.
TY - JOUR. T1 - Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression. AU - Roa, Sergio. AU - Avdievich, Elena. AU - Peled, Jonathan U.. AU - MacCarthy, Thomas. AU - Werling, Uwe. AU - Fei, Li Kuang. AU - Kan, Rui. AU - Zhao, Chunfang. AU - Bergman, Aviv. AU - Cohen, Paula E.. AU - Edelmann, Winfried. AU - Scharff, Matthew D.. PY - 2008/10/21. Y1 - 2008/10/21. N2 - Somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes are dependent upon activation-induced cytidine deaminase (AID)-induced mutations. The scaffolding properties of proliferating cell nuclear antigen (PCNA) and ubiquitylation of its residue K164 have been suggested to play an important role organizing the error-prone repair events that contribute to the AID-induced diversification of the Ig locus. We generated knockout mice for PCNA (Pcna-/-), which were embryonic lethal. Expression of PCNA with the K164R mutation rescued the lethal ...
The apolipoprotein B messenger RNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family of cytidine deaminases plays an important role in the innate immune response to viral infections by editing viral genomes. However, the cytidine deaminase activity of APOBEC3 enzymes also induces somatic mutations in host genomes, which may drive cancer progression. Recent studies of human papillomavirus (HPV) infection and disease outcome highlight this duality. HPV infection is potently inhibited by one family member, APOBEC3A. Expression of APOBEC3A and APOBEC3B is highly elevated by the HPV oncoproteins E6 and E7 during persistent virus infection and disease progression. Furthermore, there is a high prevalence of APOBEC3A and APOBEC3B mutation signatures in HPV-associated cancers. These findings suggest that induction of an APOBEC3-mediated antiviral response during HPV infection may inadvertently contribute to cancer mutagenesis and virus evolution. Here, we discuss current understanding of APOBEC3A
A variety of mutations are accumulated in the genome of HTLV-1 infected T-cells during ATL development. To elucidate the mechanism of ATL development a mouse model of ATL was established by infecting HTLV-1 to humanized NOG mice and the infected mice recapitulate the ATL-like symptoms and die of leukemia within several months of infection. Analysis of gene expressions in the humanized mouse model of ATL demonstrated the induction of APOBEC3B (A3B) gene in the HTLV-1 infected human T-cells. A3B is a member of the APOBEC family of cellular cytidine deaminase and was recently identified as the mutational source in multiple human cancers. We have previously shown that HTLV-1 infected CD25 (-) CD4 T-cells but not CD25 (+) CD4 T-cells in ATL model mouse express a small amount of Tax mRNA even though both cell populations consist of identical infected-cell clones. As the A3B expression in HTLV-1 infected CD25 (+) T-cells was similar to, or rather higher than that in CD25 (-)T-cells, Tax appears not to ...
This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008 ...
Sigma-Aldrich offers abstracts and full-text articles by [Yi Hu, Ida Ericsson, Kathrin Torseth, Stephen P Methot, Ottar Sundheim, Nina B Liabakk, Geir Slupphaug, Javier M Di Noia, Hans E Krokan, Bodil Kavli].
Bacteroides induce higher IgA production than Lactobacillus by increasing activation-induced cytidine deaminase expression in B cells in murine Peyers patches.[2009] DataPunk.Net Data INHIBITED BY Walnuts Sucralose (Splenda) Whole-grain barley β-Glucan Polymannuronic acid ENHANCED BY Stevia Low fat diets Tannic acid Gallic acid Red wine Fructo-oligosaccharides Saccharin L-citrulline Resistant starch (type IV) High meat diet ANTIBIOTIC RESISTANCE Streptogramin b …
1. Esnault C, Heidmann O, Delebecque F, Dewannieux M, Ribet D, Hance AJ, et al. APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature. 2005;433(7024):430-3. Epub 2005/01/28. doi: 10.1038/nature03238 15674295.. 2. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, et al. DNA deamination mediates innate immunity to retroviral infection. Cell. 2003;113(6):803-9. Epub 2003/06/18. doi: 10.1016/s0092-8674(03)00423-9 12809610.. 3. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003;424(6944):99-103. Epub 2003/06/17. doi: 10.1038/nature01709 12808466.. 4. Suspene R, Aynaud MM, Koch S, Pasdeloup D, Labetoulle M, Gaertner B, et al. Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo. J Virol. 2011;85(15):7594-602. Epub 2011/06/03. doi: ...
Activation-induced cytidine deaminase (AID) is critical in normal B cells to initiate somatic hypermutation and immunoglobulin class switch recombination. Accumulating evidence suggests that AID is also prooncogenic, inducing cancer-promoting mutations or chromosome rearrangements. In this context, we find that AID is expressed in |40% of primary human chronic lymphocytic leukemia (CLL) cases, consistent with other reports. Using a combination of human B lymphoid leukemia cells and mouse models, we now show that AID expression can be harnessed for antileukemic effect, after inhibition of the RAD51 homologous recombination (HR) factor with 4,4-diisothiocyanatostilbene-2-2-disulfonic acid (DIDS). As a proof of principle, we show that DIDS treatment inhibits repair of AID-initiated DNA breaks, induces apoptosis, and promotes cytotoxicity preferentially in AID-expressing human CLL. This reveals a novel antineoplastic role of AID that can be triggered by inhibition of HR, suggesting a potential new
Activation-induced cytidine deaminase (AICDA) antibody | Q9GZX7 | Activation-induced cytidine deaminase (AICDA), Cytidine aminohydrolase, AID
Overexpression of activation-induced cytidine deaminase (AID) or other cytidine deaminases causes high rates of deoxyribonucleic acid (DNA) damage (mutations, double strand DNA breaks, and chromosome rearrangements) in a high number of patients with B-cell malignancies, such as NHL, MM, and CLL, and in a subset of patients with solid tumors, such as non-small cell lung cancer (NSCLC), sarcoma, breast cancer, ovarian cancer, and squamous cell carcinoma of the head and neck. Cancer cells that overexpress AID and other cytidine deaminases rely on RAD51, a protein involved in homologous recombination, to repair the DNA damage caused by cytidine deaminases. Inhibition of RAD51 with CYT-0851 in preclinical models induces cell death, tumor growth delay or tumor regression.. The Phase 1 part of the study will follow an accelerated titration design, which includes enrollment of single patient cohorts until certain criteria are met, followed by a standard 3+3 design. This design will allow for ...
Activation induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR). AID initiates the processes that carry out immunoglobulin diversity by deaminating cytosine residues within variable (V) and switch (S) regions on the Ig locus during active transcription. The resulting G:U mispairs can then be replicated or repaired by cellular repair mechanisms to give rise to isotype-switched and antigen-specific mature antibodies.; In this study I have identified two novel phosphorylation sites, serine 41 and serine 43, and demonstrated their importance in AID activity as well as confirmed the importance of serine 38 phosphorylation. Phosphorylation null mutants generated by replacing serine with alanine are much less active than wild-type AID, as is non-phosphorylated AID purified from E. coli. In contrast, phosphorylation charge mimic mutants generated by replacing serine with aspartic acid, are (3-4) fold more active than wild-type AID. ...
Activation induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR). AID initiates the processes that carry out immunoglobulin diversity by deaminating cytosine residues within variable (V) and switch (S) regions on the Ig locus during active transcription. The resulting G:U mispairs can then be replicated or repaired by cellular repair mechanisms to give rise to isotype-switched and antigen-specific mature antibodies.; In this study I have identified two novel phosphorylation sites, serine 41 and serine 43, and demonstrated their importance in AID activity as well as confirmed the importance of serine 38 phosphorylation. Phosphorylation null mutants generated by replacing serine with alanine are much less active than wild-type AID, as is non-phosphorylated AID purified from E. coli. In contrast, phosphorylation charge mimic mutants generated by replacing serine with aspartic acid, are (3-4) fold more active than wild-type AID. ...
A significant leap forward got here in 2000 with the invention that activation-induced deaminase (AID) is actually required for hypermutation. This used to be in 2002 by means of proof that reduction without delay edits the DNA that encodes an antibody in an activated B mobile. a lot has seeing that been learnt concerning the biochemistry and rules of reduction, however the mechanism during which it truly is recruited particularly to antibody-encoding genes continues to be enigmatic. figuring out this recruitment is clinically major simply because off-target relief job at oncogenes may end up in chromosomal translocations and tumorigenesis ...
Aberrant targeting of the enzyme activation-induced cytidine deaminase (AID) results in the accumulation of somatic mutations in ∼25% of expressed genes in germinal center B cells. Observations in Ung−/− Msh2−/− mice suggest that many other genes efficiently repair AID-induced lesions, so that up to 45% of genes may actually be targeted by AID. It is important to understand the mechanisms that recruit AID to certain genes, because this mistargeting represents an important risk for genome instability. We hypothesize that several mechanisms combine to target AID to each locus. To resolve which mechanisms affect AID targeting, we analyzed 7.3 Mb of sequence data, along with the regulatory context, from 83 genes in Ung−/− Msh2−/− mice to identify common properties of AID targets. This analysis identifies three transcription factor binding sites (E-box motifs, along with YY1 and C/EBP-β binding sites) that may work together to recruit AID. Based on previous knowledge and these ...
Aberrant targeting of the enzyme activation-induced cytidine deaminase (AID) results in the accumulation of somatic mutations in ∼25% of expressed genes in germinal center B cells. Observations in Ung−/− Msh2−/− mice suggest that many other genes efficiently repair AID-induced lesions, so that up to 45% of genes may actually be targeted by AID. It is important to understand the mechanisms that recruit AID to certain genes, because this mistargeting represents an important risk for genome instability. We hypothesize that several mechanisms combine to target AID to each locus. To resolve which mechanisms affect AID targeting, we analyzed 7.3 Mb of sequence data, along with the regulatory context, from 83 genes in Ung−/− Msh2−/− mice to identify common properties of AID targets. This analysis identifies three transcription factor binding sites (E-box motifs, along with YY1 and C/EBP-β binding sites) that may work together to recruit AID. Based on previous knowledge and these ...
APOBEC proteins have evolved in mice and humans as potent innate defences against retroviral infections. APOBEC3G (hA3G) in humans and mouse APOBEC3 (mA3) deaminate cytidine in single-stranded DNA which ultimately results in hypermutation of newly synthesized proviral DNA. Other deaminase-independent mechanisms of inhibition have been identified, such as directly inhibiting reverse transcription. Both HIV and murine leukemia viruses (MuLVs) have evolved mechanisms to evade the action of the APOBEC proteins. HIV encodes the Vif protein which binds to hA3G and facilitates its rapid degradation through the proteasome. The mechanism(s) by which exogenous MuLVs evade mA3 inhibitory activity is unknown. Exogenous MuLVs encode a glycosylated gag protein (gGag) originating from an alternate CUG start site upstream of the AUG start site of the Gag structural polyproteins. gGag is synthesized to similar amounts as the structural Gag polyprotein in MuLV infected cells but is glycosylated in the endoplasmic
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However, we overlooked a mechanism natural has adopted for rapid evolution of proteins: adaptive immunity that generates a huge pool of antibodies.It is well-known that B-cells are capable of producing a large pool of new antibodies upon antigen stimuli, which is a most important protective mechanism for animals. People have been curious about the molecular mechanism of antibody generation. Recent works have revealed that an enzyme: Activation-Induced (Cytidine) Deaminase (AID) serves as an essential protein in three processes for antibody diversity, namely somatic hypermutation (SHM), class switch recombination (CSR) and gene conversion. Briefly speaking, AID converts cytidine to uracil by oxidizing the amino group to carbonyl group, resulting in mismatch of Watson-Crick base pair. Then DNA lesion repair pathways (base excision repair, BER; mismatch repair, MMR)are employed to bring DNA back to normal. In this process, the coding sequence for the hypervariable region of immunoglobulin is ...
Homo sapiens apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3D (putative) (APOBEC3D), mRNA. (H00140564-R01) - Products - Abnova
Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates somatic hypermutation (SH) and class switch recombination (CSR) by deaminating cytosine to uracil. The targeting of AID and therefore SH and CSR to Ig genes is a central process of the immune system, but the trans-acting factors mediating the specific targeting have remained elusive. Here we show that defective calmodulin inhibition of the transcription factor E2A after activation of the B cell receptor (BCR) leads to reduced BCR, IL4 plus CD40 ligand stimulated CSR to IgE and instead CSR to other Ig classes. AID that initiates CSR is shown to be in a complex with the transcription factors E2A, PAX5 and IRF4 on key sequences of the Igh locus. Calmodulin shows proximity with each of them after BCR stimulation. BCR signaling reduces binding of the proteins to some of the target sites on the Igh locus, and calmodulin resistance of E2A blocks these reductions. AID binds directly to the bHLH domain of E2A and to ...
From the host immune perspective, the generation of genomic diversity is used as both a defensive and an offensive weapon. Host mutator enzymes such as Activation-Induced Cytidine Deaminase (AID) seed diversity in the adaptive immune system by introducing targeted mutations into the immunoglobulin locus that result in antibody maturation. Related deaminases of the innate immune system can directly attack retroviral threats by garbling the pathogen genome through mutation, as accomplished by the deaminase APOBEC3G, which restricts infection with HIV. Immune mutator enzymes, however, also pose a risk to the host, as overexpression or dysregulation have been associated with oncogenesis ...
By creating an extremely diverse antibody repertoire, B cells protect the body against numerous infectious pathogens. Generation of this antibody repertoire depends on immunoglobulin gene modification events driven by four different molecular processes: V(D)J recombination, somatic hypermutation, class switch recombination, and gene conversion. The enzyme AID (activation-induced cytidine deaminase) is known to be involved in somatic hypermutation and class switch recombination. In their Perspective, Fugmann and Schatz explain that AID is also essential for gene conversion ( Arakawa et al.) and discuss how AID could operate in these three quite different processes. ...
Activation-induced cytidine deaminase (AID) is essential for two processes of immunoglobulin diversification in germinal center B cells: somatic hypermutation (SHM), in which mutations are introduced into immunoglobulin (Ig) genes, and class-switch recombination (CSR), in which genomic constant regions are recombined to encode antibodies of different isotypes. Both of these processes require AID-catalyzed C-to-U lesions at the Ig loci, which are resolved to generate point mutations or double-stranded DNA breaks in the cases of SHM and CSR, respectively. Despite over a decade of intense study, a number of open issues remain surrounding AID. The diversity of findings regarding AIDs role in DNA demethylation raises the question of the scope of its involvement in this process. Additionally, while it is clear that AID-mediated damage occurs, the effects of this damage on the average B cell have not been characterized. Finally, the issue of whether AID is able to edit RNA in vivo has never been rigorously
We have identified that autoimmune BXD2 mice exhibit unique features, including spontaneous formation of germinal centers, increased expression of activation-induced cytidine deaminase (AID), increased production of pathogenic autoantibodies that are polyreactive, significantly increased percentage of IL-17high CD4 TH cells (TH-17) and IL-17Rhigh B cells, and significantly increased numbers of type I interferon producing plasmacytoid dendritic cells in the spleens of these mice. We are currently studying the inter-connection of high IL-17, high type I IFN and the development of autoreactive B cells related to B-cell tolerance loss at the transitional stage and the germinal center stage in BXD2 mice.. We currently study the close interaction between spleen marginal zone (MZ) B cells and MZ macrophages, and the implication of disrupting this close interaction in disease relapse following B-cell depletion therapy (BCDT) in systemic lupus erythematosus (SLE). In healthy individuals, the MZ B cells ...
Our system to produce antibodies is critical for our survival against numerous infections, but it causes also many tumors. B-lymphocytes can modify their immunoglobulin (Ig) genes to generate specific antibodies with a new isotype and enhanced affinity against an antigen. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates these processes by deaminating cytosine to uracil. How somatic hypermutation (SH) and class switch recombination (CSR) are targeted is key to understanding the defect DNA integrity in lymphomas and also in other tumors where inflammatory signals aberrantly induces AID. The trans-acting factors mediating specific targeting of AID and thereby SH and CSR have remained elusive. Here we show that mutant E2A with defect inhibition by the Ca2+sensor protein calmodulin results in reduced B cell receptor- (BCR-), IL4-plus CD40 ligand-stimulated CSR to IgE and instead aberrant CSR. AID is shown to be together with the transcription factors E2A, ...
Reduced AID degradation in REG-γ−/− mice might also be expected to lead to a more general increase in genomic instability. However, REG-γ−/− mice on a normal background do not show any marked increase in tumor incidence, possibly reflecting p53 and other checkpoints (Jankovic et al., 2010). Only a small increase in the frequency of c-myc-IgH translocations was detected in cultured B cells from REG-γ-deficient (as opposed to REG-γ-proficient) mice in which AID overexpression had been induced by retroviral transduction (Fig. S3), possibly reflecting the ubiquitin-dependent degradation of such overexpressed AID (Fig. 3 D). Thus, although the results suggest that the dramatically increased class-switching in REG-γ-deficient mice is likely to be at least in part a direct consequence of the increased AID abundance, we cannot exclude the possibility that there is an additional contribution from some as yet unidentified effect of REG-γ deficiency (e.g., a perturbation of AIDs interaction ...
Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here we demonstrated that TNF-α stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via nuclear factor-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2-/-AID+, ALB-MSH2-/-, and ALB-AID+ mice in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin-producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2-/-AID+ mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation-mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. ...
Here we describe a potential new synthetic lethal therapeutic approach for the treatment of AID-expressing B cell malignancies: attenuation of RAD51-mediated HR to inhibit repair of endogenous AID-generated DSBs, culminating in cytotoxicity. This approach uses inherent recombinase activity, rather than systemically administered genotoxic agents, to induce cell-lethal genomic damage. As such, this strategy represents a special case of synthetic lethal therapy. We establish the proof of principle, showing that AID-expressing human CLL cells are hypersensitive to DIDS, a RAD51 inhibitor. Using a combination of primary patient-derived CLLs and genetic mouse models, we establish that DIDS treatment inhibits repair of AID-mediated DSBs in AID-expressing, patient-derived CLL cells. These findings establish that HR attenuation may be a therapeutically viable approach to selectively targeted treatment of cancers (and other pathologies) involving AID-expressing cells. Because AID mRNA expression is found ...
My work focuses on the etiology of autoimmune diseases affecting millions of individuals in the world by identifying molecules and pathways involved in the establishment of B-cell tolerance through the investigation of rare patients with primary immunodeficiency (PID), enrolled at Yale and through an international network.. Patients with PID provide opportunities to study the impact of specific gene defects on the regulation of B-cell tolerance and the removal of developing autoreactive B cells in humans. Using a RT-PCR based strategy that allows us to assess the frequency of autoreactive B cells, we found that alterations in B-cell receptor (BCR) signaling in patients lacking functional BTK or CD19, or mutations in molecules mediating TLR signaling such as TACI, IRAK4, MyD88 as well as in adenosine deaminase (ADA) and activation-induced cytidine deaminase (AID) all result in a defective central checkpoint and a failure to counterselect developing autoreactive B cells in the bone marrow. ...
Scientists at The Scripps Research Institute (TSRI) and Weill Cornell Medical College of have determined the first atomic-level structure of the tripartite HIV envelope protein-long considered one of the most difficult targets in structural biology and of great value for medical science.
AID (activation-induced cytidine deaminase ) er et mutator-protein som deaminerer cytosin til uracil i immunoglobulin (Ig)-genene i B-celler. AID er essensielt i vårt adaptive immunforsvar, mens feilregulert AID-aktivitet er relatert til mutasjoner og kreft. Vi har studert aktivitet, intracellulær transport og regulering av AID. For å bekjempe nye infeksjoner produserer stimulerte B celler antistoffer med økt affinitet og endrede beskyttelsesfunksjoner. Dette skjer ved at mutasjoner introduseres med høy frekvens i Ig-genene, og AID er proteinet som initierer disse prosessene ved å deaminere cytosin til uracil. Ved feil regulering av AID vil uracil som er generert i proto-oncogener være en tidlig og kritisk hendelse ved utvikling av B-celle lymfom. Ekspresjon, enzymatisk aktivitet og intracellulær lokalisering må derfor være nøye regulert for å unngå uønskede mutasjoner. AID er i hovedsak lokalisert til cytoplasma, og for at AID skal deaminere cytosin til uracil i Ig-genene må det ...
The natural target of AID-induced mutagenesis in normal germinal center B cells is the Ig locus, as well as several genes like BCL6, which nevertheless harbor a much lower mutation frequency (22, 23, 39). Moreover, numerous genes, including oncogenes like PAX5, PIM1, MYC, and RhoH/TTF, which undergo a low level of mutagenesis in some B cell lymphomas constitutively expressing AID (25, 40), appear to be targeted by AID in normal B cells, but are spared from mutations caused by error-free repair (24). Deliberate overexpression of AID has been shown to increase mutation levels of several transcribed genes in both prokaryotic and mammalian cells (41-45). However, although the nuclear-restricted AID protein induces enhanced mutagenesis both in Escherichia coli and on a transfected substrate in fibroblasts, its mutagenicity in B lymphocytes is not clearly established (9, 10). We obtained inducible clones overexpressing the WT or mutant form of AID in the AICDA−/− BL2 cell line, and confirmed that, ...
Prof. McGuigan from Cardiff School of Pharmacy, UK along with Prof. Jan Balzarini of Rega Instutute for Medical Research, Belgium have reported an innovative approach to overcome the cancer Resistance mechanism using the pro-tide technology of theirs. They prepared various Nucleotide Phosphoramidates of the known anticancer drug Gemcitabine and were able to find a molecule that was resistant to cytidine deaminase-mediated […]. » Read more ...
Rabbit polyclonal antibody raised against partial recombinant human APOBEC3G. Recombinant protein corresponding to human APOBEC3G. (PAB30317) - Products - Abnova
Viral replication and maturation rely on a complex interplay between viral and cellular proteins. During the replication cycles of herpesviruses, a number of host immune defense mechanisms have to be overcome and, in particular, innate immune barriers that are poorly defined so far have to be circumvented in order to achieve high efficiencies of replication and dissemination in host tissues. Previous work by Cristea et al. (20) has shown that very early during infection, pp65 and IFI16 interact at the HCMV MIEP, thereby triggering an increase in IE protein expression, which is accompanied by a concomitant decrease in antiviral cytokine production. Consistent with this observation, an increase in IFI16 expression during the first steps of HCMV infection has been reported previously by our group (16), confirming that HCMV triggers IFI16 expression with the scope of increasing IE gene expression early during infection.. Based on these observations, the aim of the present study was to investigate ...
Cytidine, Ability, Aid, Base Excision Repair, Cell, Cells, Cytidine Deaminase, Deoxycytidine, DNA, Enzymes, Excision Repair, Heat, Heat Shock Protein, Heat Shock Protein 70, Human, Shock, siRNA, Transfection
Cytidine Deaminase; Catalyzes The Modification Of Cytidine To Uridine In Vitro But Native RNA Substrates Have Not Been Identified, Localizes To Both The Nucleus And Cytoplasm
Cytidine, Aid, Cytidine Deaminase, Recombination, Immunoglobulin, Mice, B Cells, Regulation, Sperm, Perception, Oxygen, Future, and Concentration
Welcome to the Lab page for Harold C. Smith. In this page you will find information on the projects in the Smith lab and the people working in the lab. Dr. Smith is a tenured professor of biochemistry and biophysics at the University of Rochester, School of Medicine and Dentistry. Dr. Smiths primary function at the University is basic research and in this context he is fully engaged in biomedical laboratory research as well as training postdocs, graduate and undergraduate students.. The labs primary interest is understanding the composition, regulation and structure of macromolecular complexes involved in regulating gene expression at the level of messenger RNA expression and processing. Our focus is on a platform of enzymes that change the genetic code at the DNA or RNA level by deaminating cytidine to form uridine. Current data suggest that this family of cytidine deaminase function with other proteins (auxiliary proteins) as holoenzymes complexes which we refer to as editosomes (for RNA) or ...
Some people diagnosed with AIDS may not be stricken with the killer disease and probably are suffering from other illnesses misdiagnosed as the immune system disorder, a specialist reports.I call
Complete information for CDA gene (Protein Coding), Cytidine Deaminase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for APOBEC3B gene (Protein Coding), Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The host restriction factor Smc6 (green) is located within the nucleus (blue) of uninfected human hepatocytes. In contrast, Smc6 is not present in HBV-infected hepatocytes (red). This confocal microscopy data provides direct evidence that Smc6 is degrades during HBV infection.
AIDS is one of the deadliest human diseases ever, killing millions of people each year. Worldwide, AIDS claims approximately 5 lives every minute of every day. Learn how the AIDS virus attacks the body.