Aen, short for Apoptosis-enhancing nuclease, is a member of the DEDDh exonuclease family and shares close evolutionary relationships with the interferon-stimulated gene 20 protein (ISG20) homologs in humans [1,2]. It is a nuclear exonuclease that can target both single-and double-stranded DNA and RNA. Aen is a direct target gene of p53, and its expression is regulated by the phosphorylation status of p53. It plays a crucial role in p53-dependent apoptosis, and also has potential functions in the immune response [1,2].

In a study on Porcine epidemic diarrhea virus (PEDV) infection in MARC-145 cells, Aen expression was significantly upregulated upon PEDV strain 85-7 infection, but the amount of AEN protein decreased as viral replication increased. PEDV nsp1 and nsp5 mediated this decrease, suggesting Aen was not conducive to virus replication. Aen and its exonuclease-inactive mutant AEN-4A could induce an increase in the transcription levels of IFN-α, IFN-β, and ISGs, and AEN-4A had a higher induction ability. Overexpression of Aen and AEN-4A showed reduced or complete loss of antiviral activity in IFN-β knockdown or IFN-deficient cells, indicating Aen may activate the type-I IFN immune response to inhibit PEDV replication [1]. Another study reported that Aen is an important downstream mediator of p53 in apoptosis induction. Aen can induce apoptosis by itself, and its conserved domains are essential for both its nuclease activity and apoptosis-inducing ability. It translocates from the nucleolus to nucleoplasm upon apoptosis induction and is required for efficient DNA fragmentation in p53-dependent apoptosis [2].

In conclusion, Aen has key functions in apoptosis induction as a downstream mediator of p53 and in inhibiting viral replication by activating the type-I IFN immune response. These findings from in vitro cell-based models contribute to our understanding of its role in virus-host interactions and apoptotic processes. The study of Aen provides insights into potential mechanisms underlying certain disease conditions related to apoptosis dysregulation and viral infections [1,2].

References:

1. Luo, Miao, Ma, Jiale, Pan, Xinming, Zhang, Xinqin, Yao, Huochun. 2023. AEN Suppresses the Replication of Porcine Epidemic Diarrhea Virus by Inducing the Expression of Type I IFN and ISGs in MARC-145 Cells. In Pathogens (Basel, Switzerland), 13, . doi:10.3390/pathogens13010024. https://pubmed.ncbi.nlm.nih.gov/38251332/

2. Kawase, T, Ichikawa, H, Ohta, T, Ohki, R, Taya, Y. 2008. p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis. In Oncogene, 27, 3797-810. doi:10.1038/onc.2008.32. https://pubmed.ncbi.nlm.nih.gov/18264133/