AIMing 2 detect foreign DNA.
Foreign genomic DNA can be detected by immune cells in the cytoplasm, triggering reactions such as cell death and secretion of proinflammatory cytokines, including interleukin 1beta (IL-1beta). Several studies have now elucidated the mechanism for this response. The HIN-200 (hematopoietic interferon-inducible nuclear proteins with a 200-amino acid repeat) family member AIM2 (absent in melanoma 2) binds and oligomerizes on cytoplasmic DNA through a HIN domain. The oligomerized AIM2 recruits the adaptor ASC (apoptosis-associated specklike protein containing a CARD) through homotypic pyrin domain interactions and binds caspase-1, forming an inflammasome that generates IL-1beta. Together with previous studies, this work demonstrates that immune detection of foreign nucleic acids occurs through several distinct signaling pathways, leading to diverse immune outcomes.
Krieg
Arthur M
AM
Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA. arthur.krieg@pfizer.com
D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins / Q000378:metabolism*
C410167:AIM2 protein, human; D001704:Biopolymers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA