Disease relevance of AICDA

• Infection of human B cells with Epstein-Barr virus (EBV) was seen to result in activation-induced cytidine deaminase (AID) and polymerase-eta (pol-eta) gene expression [1].
• Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas [2].
• Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone [3].
• Activation-induced cytidine deaminase expression in follicular lymphoma: association between AID expression and ongoing mutation in FL [4].
• Presence of somatic hypermutation and activation-induced cytidine deaminase in acute lymphoblastic leukemia L2 with t(14;18)(q32;q21) [5].

High impact information on AICDA

• Particularly exciting has been the discovery of a putative RNA editing enzyme, the activation-induced cytidine deaminase (AID), that is required for all immunoglobulin gene-specific modification reactions (somatic hypermutation, class switch recombination, and gene conversion) [6].
• The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family [7].
• In addition, they reduce the density of Arp2/3-dependent actin filament branches and bind Profilin at sites of actin polymerization [8].
• Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas [9].
• All three processes depend on activation-induced cytidine deaminase (AID), a B-cell-specific protein that has been proposed (because of sequence homology) to function by RNA editing [10].

Chemical compound and disease context of AICDA

• Rac1 may act via Arp2/3, phosphatidylinositol 4,5-bisphosphate and capping-proteins in the formation of nascent phagosomes during Yersinia uptake [11].

Biological context of AICDA

• Defects in AICDA result in a hyper-IgM phenotype and lack of IgG, IgA, and IgE in both human beings and mice [12].
• BACKGROUND: Activation-induced cytidine deaminase (AICDA) is a recently identified RNA-editing deaminase that plays an important role in class-switching [12].
• In RT-PCR experiments, we found 2 novel splice variants of AICDA, one lacking all of exon 4 (variant 1; 367 base pairs) and the other lacking the first 30 base pairs of exon 4 (variant 2; 453 base pairs) [12].
• Single nucleotide polymorphism of AICDA was also investigated [13].
• Each approach identified activation-induced cytidine deaminase (AICDA) and BCL6 as targets of transcriptional activation [14].

Anatomical context of AICDA

• Activation-induced cytidine deaminase (AID), which is specifically expressed in germinal center centroblasts, is indispensable for this process [15].
• Cytidine deaminase in human white blood cells has three electrophoretic phenotypes representing the homozygous and heterozygous expression of two common alleles, CDA1 and CDA2, at an autosomal locus [16].
• It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa [17].
• The Peyer's patches in CD40(-/-) mice expressed unexpectedly high levels of activation-induced cytidine deaminase mRNA and germline alpha transcripts, but few postswitch circular DNA transcripts, arguing against significant IgA CSR [18].
• Whereas all of the classical sites for IgA CSR in the GALT in CD40(-/-) mice appeared severely compromised for IgA CSR, B cells in the peritoneal cavity demonstrated the expression of activation-induced cytidine deaminase mRNA comparable to that of wild-type mice [18].

Associations of AICDA with chemical compounds

• Class-switch recombination (CSR), somatic hypermutation (SHM), and antibody gene conversion are distinct DNA modification reactions, but all are initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA [19].
• Deoxyuridine is generated preferentially in the nontranscribed strand of DNA from cells expressing activation-induced cytidine deaminase [20].
• Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming [21].
• Finally, PIP2 also stimulates the transient, direct binding interaction of the Arp2/3 complex with vinculin and thus may couple adhesion to actin assembly [22].
• Both SHM and CSR are initiated by activation-induced cytidine deaminase (AID), which deaminates deoxycytidine to deoxyuridine in single-stranded DNA (ssDNA) [23].

Regulatory relationships of AICDA

• E2-CD81 interaction on B cells triggered the enhanced expression of activation-induced cytidine deaminase (AID) and also stimulated the production of tumor necrosis factor alpha [24].

Other interactions of AICDA

• Neither the IFNG intron 1 CA repeat nor 465C/T of AICDA showed any association with asthma [13].
• And human epithelial cancers possess the essential effectors including RAG-1 and RAG-2, but not activation induced cytidine deaminase (AID) protein [25].
• Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NFkappaB [26].
• These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China [27].
• Polymorphisms of IL-4, IL-4R alpha, and AICDA genes in adult allergic asthma [27].

Analytical, diagnostic and therapeutic context of AICDA

• Sequence analysis revealed ongoing Smu deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase-dependent somatic mutations [28].
• Quantitative real-time PCR and immunohistochemical stainings for activation-induced cytidine deaminase, which is indispensable for SHM, demonstrated significantly higher expression in PCLBCL, leg type [29].
• Immunoprecipitation reactions indicate that myoB and myoC form a complex with p116, Arp2/3, and capping protein in vivo, that the myosins bind to p116 through their SH3 domains, and that capping protein and the Arp2/3 complex in turn bind to p116 [30].
• We used radiolytic protein footprinting with mass spectrometry in solution to probe the effects of nucleotide- and WASp-binding on Arp2/3 [31].
• We also found that expression of activation-induced cytidine deaminase (AID), which is required for CSR and somatic hypermutation, was detectable by RT-PCR in 4 of 10 cases and by immunohistochemistry in one of three cases analyzed [32].

References