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ABSTRACT
Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.
| Abbreviations | ||
| Ab-MLV | = | Abelson murine leukemia virus |
| AID | = | Activation-induced deaminase |
| APOBEC1 | = | Apolipoprotein B mRNA-editing cytidine deaminase catalytic polypeptide 1 |
| BCL | = | B-cell lymphoma |
| BL | = | Burkitt's lymphoma |
| ChiP | = | Chromatin immunoprecipitation |
| CRM-1 | = | Chromosome region maintenance/exportin 1 |
| CTNNBL-1 | = | Catenin beta-like 1 |
| CSR | = | Class-switch recombination |
| DIVAC | = | Diversification activator |
| DLBCL | = | Diffuse large B-cell lymphoma |
| dC | = | Deoxycytidine |
| dU | = | Deoxyuracil |
| EBV | = | Epstein-Barr virus |
| eEF1A | = | Eukaryotic translation elongation factor 1α |
| FL | = | Follicular lymphoma |
| GANP | = | Germinal center-associated nuclear protein |
| GCV | = | Gene conversion |
| GFP | = | Green fluorescent protein |
| HCC | = | Hepatocellular carcinoma |
| HCV | = | Hepatitis C virus |
| HIGM | = | Hyper IgM syndrome |
| Hsp | = | Heat shock protein |
| HP1 | = | Heterochromatin protein 1 |
| IFN-γ | = | Interferon-γ |
| Ig | = | Immunoglobulin |
| ILs | = | Interleukins |
| KAP | = | KRAB domain-associated protein 1 |
| KSHV | = | Kaposi's sarcoma-associated herpesvirus |
| LMP-1 | = | Latent membrane protein-1 |
| MYC | = | v-myc avian myelocytomatosis viral oncogene homolog |
| NES | = | Nuclear export signal |
| NF-κB | = | Nuclear factor-κB |
| NLS | = | Nuclear localization signal |
| PAF | = | Polymerase-associated factor |
| PAX5 | = | Paired box protein 5 |
| PIM1 | = | Proto-oncogene serine/threonine-protein kinase |
| PKA | = | Protein kinase A |
| PTBP-2 | = | Polypyrimidine tract binding protein 2 |
| RAG | = | Recombination-activating gene |
| RPA | = | Replication protein A |
| SHM | = | Somatic hypermutation |
| SLE | = | Systemic lupus erythematosus |
| Spt5 | = | Suppressor of Ty5 homolog |
| SRSF | = | Serine/arginine-rich protein splicing factor |
| SSRP | = | Structure specific recognition protein 1 |
| TGF-β | = | Transforming growth factor-β |
| TLS | = | Translesion DNA synthesis |
| TNF | = | Tumor necrosis factor |
| TSS | = | Transcription start site |
| UTR | = | Untranslated region |
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
Acknowledgments
M.C. and A.T. acknowledge University Grants Commission, Govt. of India, A.K.S. acknowledges Department of Science and Technology, Govt. of India, A.J. acknowledges Council for Scientific and Industrial Research, Govt. of India, for Ph.D. research fellowships. P.K. thanks, Department of Science and Technology, Govt. of India, for the award of Ramanujan Fellowship Grant and Research Grant (EMR/2016/003547) and Department of Biotechnology, Govt. of India, for the award of Research Grant (BT/PR20319/BBE/117/189/2016).