Fig. 3.

Proposed model for the regulation and potential roles of the AIM2 in the suppression of tumorigenesis. Most cell types express constitutive low levels of AIM2 mRNA or protein. However, treatment of cells with IFNs or certain viral infections induces the expression of AIM2. The increased levels of AIM2 protein in most cell types that have been tested inhibited cell growth. Furthermore, the cell growth inhibition was dependent upon the status of p53 in cells. In the presence of cytosolic DNA, keratinocytes, fibroblasts (both young and senescent), and epithelial cells assemble the AIM2 inflammasome, resulting in the production of proinflammatory cytokines, such as IL-1β and IL-18. Increased production of proinflammatory cytokines in tissue leads to inflammation. Notably, chronic inflammation is associated with mutations in cells and the development of certain cancers. Mutations in the AIM2 gene or its reduced expression in cells due to hypermethylation of the gene promoter is associated with the development of colorectal cancer, thus suggesting that the mutant AIM2 or the lack of its expression provides growth advantage to cancer cells. Furthermore, increased expression of POP3 in cancer cells and its heterodimerization with AIM2 could inactivate the AIM2 functions, thus leading to cell growth advantage and tumorigenesis