APOBEC3, short for apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3, is a family of cytosine deaminases. These enzymes play a crucial role in the innate immune system, capable of inhibiting a wide range of endogenous and exogenous viruses through deaminase and deaminase-independent mechanisms [3]. They are also involved in restricting the mobilization of retrotransposons [4].

In human cancer cells, deletion experiments in cell lines (functionally similar to gene-knockout in a cellular context) have shown that APOBEC3A is the main driver of APOBEC3-associated mutational signatures. Deletion of APOBEC3A diminished these signatures, and deletion of both APOBEC3A and APOBEC3B further decreased the mutation burdens but did not eliminate them. In some cell lines, deleting APOBEC3B increased APOBEC3A protein levels, activity, and mutagenesis [1].

In conclusion, APOBEC3 enzymes are essential components of the innate immune system, having antiviral and retrotransposon-restricting functions. The gene-knockout-like experiments in cancer cell lines have revealed their role in generating mutational signatures in cancer, suggesting that APOBEC3-mediated mutagenesis may contribute to cancer evolution. Understanding APOBEC3 is crucial for comprehending cancer development and potentially developing new therapeutic strategies targeting APOBEC3-related mutagenesis [1,2].

References:

1. Petljak, Mia, Dananberg, Alexandra, Chu, Kevan, Stratton, Michael R, Maciejowski, John. 2022. Mechanisms of APOBEC3 mutagenesis in human cancer cells. In Nature, 607, 799-807. doi:10.1038/s41586-022-04972-y. https://pubmed.ncbi.nlm.nih.gov/35859169/

2. Petljak, Mia, Green, Abby M, Maciejowski, John, Weitzman, Matthew D. 2022. Addressing the benefits of inhibiting APOBEC3-dependent mutagenesis in cancer. In Nature genetics, 54, 1599-1608. doi:10.1038/s41588-022-01196-8. https://pubmed.ncbi.nlm.nih.gov/36280735/

3. Sadeghpour, Shiva, Khodaee, Saeideh, Rahnama, Mostafa, Rahimi, Hamzeh, Ebrahimi, Diako. 2021. Human APOBEC3 Variations and Viral Infection. In Viruses, 13, . doi:10.3390/v13071366. https://pubmed.ncbi.nlm.nih.gov/34372572/

4. Modenini, Giorgia, Abondio, Paolo, Boattini, Alessio. 2022. The coevolution between APOBEC3 and retrotransposons in primates. In Mobile DNA, 13, 27. doi:10.1186/s13100-022-00283-1. https://pubmed.ncbi.nlm.nih.gov/36443831/