Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B-cell lymphomas arising in lymph nodes and spleen of aging mice deficient in the Ung DNA glycosylase were recovered, dispersed, grown in short-term culture, and CD19-positive B-cells retrieved and analysed. Several tumors as well as controls only expressed detectable amounts of the Aid deaminase after mitogenic stimulation, as estimated by real-time PCR of transcripts. However, one unusually large lymph node tumor expressed a high level of Aid constitutively. This particular tumor also showed a substantially increased mutation frequency in the Aid gene itself as well as in the bcl-6 and c-myc genes, but not in the p53 gene, consistent with aberrant somatic hypermutation. Other B-cell lymphomas from Ung(-/-) mice exhibited a modest increase in mutation frequency.
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PMID:Mutation frequencies and AID activation state in B-cell lymphomas from Ung-deficient mice. 1573 13

The immunological targets of estrogen at the molecular, humoral, and cellular level have been well documented, as has estrogen's role in establishing a gender bias in autoimmunity and cancer. During a healthy immune response, activation-induced deaminase (AID) deaminates cytosines at immunoglobulin (Ig) loci, initiating somatic hypermutation (SHM) and class switch recombination (CSR). Protein levels of nuclear AID are tightly controlled, as unregulated expression can lead to alterations in the immune response. Furthermore, hyperactivation of AID outside the immune system leads to oncogenesis. Here, we demonstrate that the estrogen-estrogen receptor complex binds to the AID promoter, enhancing AID messenger RNA expression, leading to a direct increase in AID protein production and alterations in SHM and CSR at the Ig locus. Enhanced translocations of the c-myc oncogene showed that the genotoxicity of estrogen via AID production was not limited to the Ig locus. Outside of the immune system (e.g., breast and ovaries), estrogen induced AID expression by >20-fold. The estrogen response was also partially conserved within the DNA deaminase family (APOBEC3B, -3F, and -3G), and could be inhibited by tamoxifen, an estrogen antagonist. We therefore suggest that estrogen-induced autoimmunity and oncogenesis may be derived through AID-dependent DNA instability.
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PMID:Estrogen directly activates AID transcription and function. 1913 65

For several reasons Burkitt's lymphoma (BL) has become a paradigm in cancer research: for its particular geographical distribution, the presence of Epstein-Barr virus (EBV) in the cases in high incidence areas, and for the activation of the proto-oncogene c-myc by chromosomal translocation in one of the immunoglobulin gene loci. As c-MYC activates both, proliferation and apoptosis, at least two events have to cooperate in lymphomagenesis: activation of c-MYC and a shift in the balance from apoptosis towards survival. Antigenic and/or polyclonal stimulation of the B cell receptor, genetic instability imposed by activation induced deaminase (AID), as well as the viral gene products EBNA1 and several small non-coding non-polyadenylated RNAs are the main factors suspected to play an important role in the pathogenesis of BL. Despite intensive research, the role of the virus has remained largely elusive in the past decades, but the discovery of two viral microRNA clusters that are expressed in EBV associated tumors including BL has raised new hopes and expectations that EBV is going to reveal its mystery. This review focuses on the interplay between cellular and viral factors and puts special emphasis on mouse models and experimental cell culture systems that address these points.
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PMID:Epstein-Barr virus and its role in the pathogenesis of Burkitt's lymphoma: an unresolved issue. 1961 54

Background The Nuclear Factor kappaB (NF-kB) family consists of transcription factors that play a complex and essential role in the regulation of immune responses and inflammation. NF-kB has recently generated considerable interest as it has been implicated in human cancer initiation, progression and resistance to treatment. In the present comprehensive review the different aspects of NF-kB signaling in the carcinogenesis of cancer of the uterine cervix are discussed. NF-kB functions as part of a network, which determines the pattern of its effects on the expression of several other genes (such as crosstalks with reactive oxygen species, p53, STAT3 and miRNAS) and thus its function. Activation of NF-kB triggered by a HPV infection is playing an important role in the innate and adaptive immune response of the host. The virus induces down regulation of NF-kB to liquidate the inhibitory activity for its replication triggered by the immune system leading a status of persistant HPV infection. During the progression to high grade intraepithelial neoplasia and cervical cancer NF-KB becomes constitutionally activated again. Mutations in NF-kB genes are rare in solid tumors but mutations of upstream signaling molecules such as RAS, EGFR, PGF, HER2 have been implicated in elevated NF-kB signaling. NF-kB can stimulate transcription of proliferation regulating genes (eg. cyclin D1 and c-myc), genes involved in metastasis, VEGF dependent angiogenesis and cell immortality by telomerase. NF-kB activation can also induce the expression of activation-induced cytodine deaminase (AID) and the APOBEC proteins, providing a mechanistic link between the NF-kB pathway and mutagenic characteristic of cervical cancer. Inhibition of NF-kB has the potential to be used to reverse resistance to radiotherapy and systemic anti-cancer medication, but currently no clinicaly active NF-kB targeting strategies are available.
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PMID:The role of Nuclear Factor-kappa B signaling in human cervical cancer. 2919 28