APOBEC3H (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3H)

Consistent with tumor data, RNA-seq showed upregulation of tumor enhancing pathways only in cells that enhanced tumor progression. The results indicate that in a breast cancer xenograft model, APOBEC3A and APOBEC3H Haplotype I are more likely to contribute to enhanced tumor progression than APOBEC3B.

Functional studies revealed that inhibition of the mutated oncogene ROS1 using crizotinib induces death in infected leukocytes, confirming its role in transformation...Our findings provide new insights into how T. annulata reprograms host cells through genomic instability and mutations, identifying ROS1 and TP53 as critical targets for therapeutic intervention. This work advances understanding of parasite-induced oncogenic transformation and offers pathways for future research.

These study findings suggest that APOBEC3 genes are commonly overexpressed in ccRCC, and their expression levels are associated with poor prognosis in ccRCC, somatic gene mutations, cancer immunomodulation, and immune cell infiltration levels in the tumor microenvironment.

A conversion formula was applied to translate these protein-protein interaction energies to a comparable scale for non-protein interactions, further underscoring the superior binding potential of apigenin and luteolin. These findings highlight the therapeutic promise of these natural compounds in preventing HPV-16-induced oncogenesis, warranting further experimental validation for clinical applications.

Surprisingly, APOBEC3C lacks the bias for the lagging strand of DNA replication that is seen for APOBEC3A and APOBEC3B. The unique preferences of APOBEC3C constitute a mutation profile that will be useful in defining sites of APOBEC3C mutagenesis in human genomes.

Altogether, the results uncover novel functions and interactions of the APOBEC3 family and suggest they may have fundamental roles in cellular RNA biology, their protein-protein interactions are not redundant, and there are protein-protein interactions with tumor suppressors, suggesting a role in cancer biology. Data are available via ProteomeXchange with identifier PXD044275.

The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir...Although the vast majority of APOBEC3A- and APOBEC3B-induced single base substitution mutations occur outside of predicted chromosomal DNA hairpin structures, whole genome sequence analyses and supporting biochemical studies also indicate that both enzymes are capable of deaminating the single-stranded loop regions of DNA hairpins at elevated rates. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both APOBEC3A and APOBEC3B.

Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes are contributing in a combinatorial manner to the overall mutation landscape. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both enzymes.

We further reveal an expression pattern of APOBECs in a large Finnish MCC sample cohort. Thus, the findings presented here suggest a molecular mechanism underlying an aggressive carcinoma with poor prognosis.