Absent in melanoma 2 (AIM2) (AIM2)

Absent in melanoma 2 (AIM2) is a cytosolic pattern recognition receptor that serves as a critical sensor for double-stranded DNA (dsDNA) of both microbial and host origin [1, 3]. Upon binding to dsDNA via its C-terminal HIN-200 domain, AIM2 undergoes a conformational change that allows its N-terminal pyrin domain (PYD) to recruit the adaptor protein ASC, leading to the assembly of the AIM2 inflammasome [5, 6]. This macromolecular complex activates caspase-1, which subsequently processes the pro-inflammatory cytokines IL-1β and IL-18 into their active forms and cleaves gasdermin D to induce pyroptosis, a lytic form of programmed cell death [1, 6]. AIM2 plays a dual role in human health: it is essential for host defense against DNA viruses and intracellular bacteria, yet its aberrant activation by self-DNA is implicated in autoimmune and inflammatory conditions such as systemic lupus erythematosus, psoriasis, and neurodegenerative diseases [3, 4, 7]. In oncology, AIM2 acts as a tumor suppressor in colorectal cancer and melanoma but may promote progression in other cancers like non-small cell lung cancer [5, 11]. Therapeutic strategies targeting AIM2 include small molecule inhibitors like suramin and inhibitory oligonucleotides (e.g., ODN A151) that compete for DNA binding, offering potential treatments for DNA-driven inflammatory pathologies [8, 9].

Other names

Interferon-inducible protein AIM2PYHIN4

Competitive inhibition of double-stranded DNA binding to the HIN domain and disruption of inflammasome assembly [8, 9].