Activation-induced cytidine deaminase (AID): single activity – pleiotropic effect

Activation-induced cytidine deaminase (AID) plays an essential role in the generation of a highly competent repertoire

of antibodies by participating in class switch recombination (CSR) and somatic hypermutation (SHM). After

B cell stimulation by antigens, AID initiates SHM and CSR by deamination of cytidine to uridine in the variable

and constant regions of Ig genes. An adverse effect of AID’s ability to directly modify genome sequences is its

mutagenic potential. AID has been shown to occasionally target non-Ig genes and its abnormal expression is

strongly associated with tumorigenesis. Aberrant AID expression can also be triggered by some oncogenic pathogens,

such as Helicobacter pylori and several viruses. The latest reports show that also under physiological conditions

AID might act beyond the immune system. Data exist suggesting that AID can play a role in the process

of active genome demethylation – the heart of epigenetic gene activation and reprogramming. Moreover, it has

been shown that abnormal genome demethylation mediated by AID might be associated with human colon cancers.

The potential role of AID in the active demethylation process is still controversial, but the hypothesis that

aberrant AID expression may cause cancerogenesis by changing genome methylation patterns appears highly

attractive. As a unique human enzyme able to induce both genetic and epigenetic alterations under physiological

and pathological conditions, AID could be a promising and versatile drug target. In this review we present the

current state of knowledge on this topic and the controversies surrounding the pleiotropic effect of AID function.