Biology:AIM2
 Generic protein structure example |
Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene.[1][2] Recent research has shown that AIM2 is part of the inflammasome and contributes to the defence against bacterial and viral DNA.[3]
Structure
AIM2 is a 343 amino acid protein with a N-terminal DAPIN (or pyrin) domain (amino acids 1-87) and a C-terminal HIN-200 domain (amino acids 138-337), which is known to have two oligonucleotide-binding folds.[4]
Function
AIM2 is a member of the Ifi202/IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2.[2]
Though there has been virtually no biochemistry performed, a model based on cell-based or in vivo experiments has led to the current model of how AIM2 triggers the inflammasome. The C-terminal HIN domain binds double stranded DNA (either viral, bacterial, or even host) and acts as a cytosolic dsDNA sensor. This leads to the oligomerization of the inflammasome complex. The N-terminal pyrin domain of AIM2 interacts with the pyrin domain of another protein ASC (or Apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain). ASC also contains a CARD domain (caspase activation and recruitment domain), that recruits procaspase-1 to the complex. This leads to the autoactivation of caspase-1, an enzyme that processes proinflammatory cytokines (IL-1b and IL-18).[3] AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity.[5]
Clinical relevance
Elevated levels of AIM2 expression are found in skin cells from people with psoriasis.[6] In systemic lupus erythematosus, lysosome dysfunction allows DNA to gain access to the cytosol and activate AIM2 resulting in increased type 1 interferon production.[7]
References
- ↑ "Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma". Oncogene 15 (4): 453–7. Aug 1997. doi:10.1038/sj.onc.1201206. PMID 9242382.
- ↑ 2.0 2.1 "Entrez Gene: AIM2 absent in melanoma 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9447.
- ↑ 3.0 3.1 "The inflammasomes". Cell 140 (6): 821–32. March 2010. doi:10.1016/j.cell.2010.01.040. PMID 20303873.
- ↑ "AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA". Nature 458 (7237): 509–13. March 2009. doi:10.1038/nature07710. PMID 19158676. Bibcode: 2009Natur.458..509F.
- ↑ "AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity". Proceedings of the National Academy of Sciences of the United States of America 113 (32): E4671-80. August 2016. doi:10.1073/pnas.1602419113. PMID 27462105.
- ↑ "Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions". Science Translational Medicine 3 (82): 82ra38. May 2011. doi:10.1126/scitranslmed.3002001. PMID 21562230.
- ↑ "Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus". Proceedings of the National Academy of Sciences of the United States of America 113 (15): E2142-51. April 2016. doi:10.1073/pnas.1513943113. PMID 27035940. Bibcode: 2016PNAS..113E2142M.
External links
- Human AIM2 genome location and AIM2 gene details page in the UCSC Genome Browser.
Further reading
- "The Ifi 200 genes: an emerging family of IFN-inducible genes". Biochimie 80 (8–9): 721–8. 1999. doi:10.1016/S0300-9084(99)80025-X. PMID 9865494.
- "The putative tumor suppressor AIM2 is frequently affected by different genetic alterations in microsatellite unstable colon cancers". Genes Chromosomes Cancer 46 (12): 1080–9. 2007. doi:10.1002/gcc.20493. PMID 17726700.
- "AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model". Mol. Cancer Ther. 5 (1): 1–7. 2006. doi:10.1158/1535-7163.MCT-05-0310. PMID 16432157.
- "Biochemical and growth regulatory activities of the HIN-200 family member and putative tumor suppressor protein, AIM2". Biochem. Biophys. Res. Commun. 326 (2): 417–24. 2005. doi:10.1016/j.bbrc.2004.11.048. PMID 15582594.
- "AIM-2: a novel tumor antigen is expressed and presented by human glioma cells". J. Immunother. 27 (3): 220–6. 2004. doi:10.1097/00002371-200405000-00006. PMID 15076139.
- "Cytoplasmic localization of the interferon-inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200-gene family". FEBS Lett. 474 (1): 38–42. 2000. doi:10.1016/S0014-5793(00)01571-4. PMID 10828447.
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