AIM2

AIM2 (AIM2 stands for "Absent In Melanoma 2") is a protein encoded by the AIM2 gene, which is located on chromosome 1q23.1-q23.2. AIM2 is a member of the IFI20X/IFI16 family. It plays a putative role in the control of cell proliferation. Interferon-gamma induces the expression of AIM2.

The protein is involved in the innate immune response by recognizing cytosolic double-stranded DNA and inducing caspase-1-activating inflammasome formation in macrophages (Woerner SM et al.2007; Tsuchiya K et al. 2010). After binding to DNA, the AIM2 protein is thought to undergo oligomerization and associate with PYCARD, thereby initiating the recruitment of the caspase-1 precursor and the processing of interleukin-1 beta and interleukin-18 (Hornung V et al. 2009).

AIM2 recognizes cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner (Fernandes-Alnemri T et al. 2009). Also acts as a mediator of pyroptosis/necroptosis and apoptosis (panoptosis) in response to bacterial infection. It can also trigger PYCARD-dependent, caspase-1-independent cell death, in which caspase-8 (see caspases below) is involved. AIM2 is active as a tumor suppressor and may act by suppressing NF-kappa-B transcriptional activity.

AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common PFAS, and trigger IL-1β secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome (see also inflammasome) in a process that involves the release of mitochondrial DNA via the Ca2+-PKC-NF-κB/JNK-BAX/BAK axis (Wang LQ et al. 2022).

1. Fernandes-Alnemri T et al. (2009) AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458:509-513.
2. Hornung V et al. (2009) AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514-518.
3. Tsuchiya K et al. (2010) Involvement of absent in melanoma 2 in inflammasome activation in macrophages infected with Listeria monocytogenes. J Immunol 185:1186-1195.
4. Wang LQ et al. (2022) Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome. Nat Commun. 2021 May 18;12(1):2915. doi: 10.1038/s41467-021-23201-0. Erratum in: Nat Commun 13: 5667.
5. Woerner SM et al.(2007) The putative tumor suppressor AIM2 is frequently affected by different genetic alterations in microsatellite unstable colon cancers. Genes Chromosomes Cancer 46:1080-1089.