AIM2 Protein, Human

AIM2 protein serves as a crucial sensor component within the AIM2 inflammasome, orchestrating inflammasome activation in response to the presence of cytosolic double-stranded DNA (dsDNA), ultimately leading to pyroptosis. This supramolecular complex assembles in the cytosol as a response to pathogens and damage-associated signals, playing pivotal roles in innate immunity and inflammation. AIM2 acts as a pattern recognition receptor (PRR), specifically binding and recognizing dsDNA in the cytosol, thus facilitating the formation of the inflammasome polymeric complex composed of AIM2, CASP1, and PYCARD/ASC. Activation of pro-caspase-1 by the AIM2 inflammasome leads to the cleavage and activation of inflammatory cytokines IL1B and IL18, as well as gasdermin-D (GSDMD), promoting cytokine secretion. AIM2 detects cytosolic dsDNA in a non-sequence-specific manner, responding to viral and bacterial origin. Furthermore, AIM2 plays a role in the DNA damage response, mediating pyroptosis in response to double-strand DNA breaks caused by acute ionizing radiation. In the context of neurodevelopment, AIM2 acts as a regulator, promoting neural cell death in response to DNA damage in the developing brain. Independently, AIM2 serves as a tumor suppressor by restricting stem cell proliferation in the intestinal mucosa, inhibiting the AKT-mTOR signaling pathway, and regulating regulatory T-cell (Treg) homeostasis to restrain autoimmune diseases. AIM2's multifaceted functions encompass its role in inflammatory responses, DNA damage sensing, and regulation of cell proliferation, highlighting its significance in host defense and cellular homeostasis.