Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3A (APOBEC3A) (APOBEC3A)

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3A (APOBEC3A) is a potent DNA cytidine deaminase that serves as a critical component of the human innate immune system. Its primary physiological role involves restricting the replication of foreign genetic elements, including retroviruses like HIV-1 and DNA viruses such as HPV and HBV, by catalyzing the deamination of cytosine to uracil in single-stranded DNA (ssDNA) [6, 10, 13]. This enzymatic activity induces lethal hypermutations in viral genomes, effectively thwarting their integration and replication [7, 10]. However, aberrant expression of APOBEC3A can lead to the deamination of the host's own genomic DNA, resulting in characteristic mutational signatures (SBS2 and SBS13) that drive tumor evolution and genomic instability in various cancers, including lung, breast, and pancreatic tumors [1, 18]. In the context of oncology, APOBEC3A is a key driver of therapeutic resistance, particularly against targeted therapies like tyrosine kinase inhibitors, by facilitating the acquisition of secondary resistance mutations [5, 12]. Current therapeutic research is focused on developing small-molecule and oligonucleotide-based inhibitors to suppress its mutagenic activity and improve clinical outcomes in cancer patients [2, 3].

Other names

A3AARP3PHRBNPhorbolin-1bK150C2.1DNA dC->dU-editing enzyme APOBEC-3A

Inhibition of cytidine deaminase activity to prevent host genome mutagenesis and genomic instability.