Exploring APOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer

• DOI: 10.1016/j.isci.2022.105077
• Publication Date: 2022-09-05T07:24:54Z
• Authors: Christina Papini; Zechen Wang; Shalley N. Kudalkar; Travis Parke Schrank; Su Tang; Tomoaki Sasaki; Cory Wu; Brandon Tejada; Samantha J. Ziegler; Yong Xiong; Natalia Issaeva; Wendell G. Yarbrough; Karen S. Anderson
• Keywords: Cytidine

APOBEC3 family members are cytidine deaminases catalyzing conversion of to uracil. Many studies have established a link between expression and cancer development progression, especially APOBEC3A (A3A) APOBEC3B (A3B). Preclinical with human papillomavirus positive (HPV+) head neck squamous cell carcinoma (HNSCC) clinical trial specimens revealed induction A3B, but not A3A after demethylation. We examined the kinetic features deaminase activity for full length A3B found that longer substrates purine at -2 position favored by whereas prefers shorter an adenine or thymine position. The importance biological significance catalytic rather than preference was also in HPV+ HNSCCs. Our study explored factors influencing formation A3B-related mutations essential understanding APOBEC3-related carcinogenesis facilitating drug discovery.