Apobec3, short for apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3, is a family of cytosine deaminases. These enzymes play crucial roles in the innate immune system, capable of inhibiting a wide range of endogenous and exogenous viruses via deaminase-dependent and-independent mechanisms [2]. They are also involved in restricting the mobilization of retrotransposons in primates [3].

In human cancer cells, deletion experiments in cell lines (functionally similar to gene knockout in models) have provided insights. Deletion of APOBEC3A diminished APOBEC3-associated mutational signatures, and deletion of both APOBEC3A and APOBEC3B further decreased APOBEC3 mutation burdens but did not eliminate them. In some cell lines, deletion of APOBEC3B increased APOBEC3A protein levels, activity, and APOBEC3A-mediated mutagenesis. These suggest APOBEC3A is a main driver of APOBEC3-related mutations in cancer, and APOBEC3B can both contribute to and restrain mutagenesis [1].

In summary, Apobec3 is essential for antiviral defense and retrotransposon restriction. Model-based research, like the gene-deletion experiments in cancer cell lines, reveals its complex role in cancer mutagenesis. Understanding Apobec3's functions helps in comprehending viral-host interactions and cancer evolution, potentially offering new strategies for treating virus-related diseases and cancers associated with APOBEC3-mediated mutagenesis.

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. 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/

3. 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/