It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function.
![icad apoptosis icad apoptosis](https://media.springernature.com/full/springer-static/image/art%3A10.1186%2Fs13578-016-0103-9/MediaObjects/13578_2016_103_Fig7_HTML.gif)
The current study therefore provides novel insights into the anti-viral immune response of mud crabs. One of the nucleases primarily responsible for genomic DNA fragmentation during apoptosis is called DNA Fragmentation Factor 40 (DFF40) or Caspase-activated DNase (CAD). DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. Moreover, our results showed that virus infection could activate SpICAD to reduce the apoptosis rate of hemocyte, which eventually contribute to WSSV replication in mud crab. In this study, SpICAD identified in mud crab ( Scylla paramamosain) was characterized, we found that the expression of SpICAD was upregulated during WSSV (White Spot Syndrome Virus) infection in mud crab, then, the role of SpICAD in immunoregulation was further explored via RNAi approach, the data revealed that SpICAD could inhibit caspase signaling and mitochondrial membrane potential (⊿ψm) and thus suppress apoptosis process. Upon apoptosis induction, CAD is released from the complex by the caspase-3-mediated cleavage of ICAD, and catalyzes nucleosomal DNA fragmentation in dying cells. However, the involvement of ICAD during virus infection has not been addressed in invertebrates. Thus the CIDE-N domain represents a novel class of regulatory domains that can control the function of adjacent domains.
![icad apoptosis icad apoptosis](https://www.genetex.com/upload/website/prouct_img/normal/GTX31635/GTX31635_230_ICC-IF_20180221_18121410_966.jpg)
In addition, deletion of the CIDE-N domain results in enhanced apoptosis, supporting its role as a regulatory domain.
![icad apoptosis icad apoptosis](https://cshperspectives.cshlp.org/content/6/6/a016394/F1.large.jpg)
ICAD is the inhibitor of caspase-activated deoxyribonuclease and has been widely investigated for its apoptotic regulatory function in higher animals, whereas apoptosis is tightly relevant to immune defense. In this protein, the CIDE-N domain is required for DFF45/ICAD inhibition of CIDE-A-mediated apoptosis.