Structures and functions of APOBEC family members and their roles in disease control

Abstract:

Activation induced cytidine deaminase (AID) and apolipoprotein B mRNA editing enzyme catalytic peptide (APOBEC) constitute a conserved family of cytidine deaminase enzymes. The family members have different functions in the body, and they play an important role in the immune defense of the host. AID plays a role mainly in the adaptive immune systems of vertebrates, mediating class switch recombination, antibody affinity maturation, and antibody diversity generation. APOBEC1 capable of catalyzing cytosine deamination, mediating RNA editing for cellular regulation, and resisting retroviral infection is involved in tumorigenesis and cancer development. APOBEC2, most abundant in cardiac and skeletal muscle, is associated with muscle fiber type switch, loss of weight, muscle development, and myopathy. Moreover, it may have potential indirect effects in controlling gene expression. APOBEC3s play key roles in both innate and adaptive immune responses. They are involved in the inhibition of retrotransposon functioning and viral infection, DNA degradation, RNA editing, and cell cycle regulation. The APOBEC4 gene is conserved in various animal species, with the active center sequence different from those of other APOBEC proteins. It is widely recognized that APOBEC4 is a uridine-editing enzyme, which has antiviral activity. The research is limited regarding the animal-derived APOBEC family members. This review describes the structural characteristics and biological functions of APOBEC family members, providing reference for research on the roles of animal-derived APOBEC family members in the immune responses and disease control. In addition, this review provides new ideas for the development of antivirals by enhancing the activities of APOBEC family members.