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词条 AIM2
释义

  1. Structure

  2. Function

  3. Clinical relevance

  4. References

  5. External links

  6. Further reading

{{Infobox_gene}}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

1. ^{{cite journal | vauthors = DeYoung KL, Ray ME, Su YA, Anzick SL, Johnstone RW, Trapani JA, Meltzer PS, Trent JM | title = Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma | journal = Oncogene | volume = 15 | issue = 4 | pages = 453–7 | date = Aug 1997 | pmid = 9242382 | pmc = | doi = 10.1038/sj.onc.1201206 }}
2. ^1 {{cite web | title = Entrez Gene: AIM2 absent in melanoma 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9447| accessdate = }}
3. ^1 {{cite journal | vauthors = Schroder K, Tschopp J | title = The inflammasomes | journal = Cell | volume = 140 | issue = 6 | pages = 821–32 | date = March 2010 | pmid = 20303873 | doi = 10.1016/j.cell.2010.01.040 }}
4. ^{{cite journal | vauthors = Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES | title = AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA | journal = Nature | volume = 458 | issue = 7237 | pages = 509–13 | date = March 2009 | pmid = 19158676 | pmc = 2862225 | doi = 10.1038/nature07710 }}
5. ^{{cite journal | vauthors = Di Micco A, Frera G, Lugrin J, Jamilloux Y, Hsu ET, Tardivel A, De Gassart A, Zaffalon L, Bujisic B, Siegert S, Quadroni M, Broz P, Henry T, Hrycyna CA, Martinon F | title = AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 32 | pages = E4671-80 | date = August 2016 | pmid = 27462105 | pmc = 4987819 | doi = 10.1073/pnas.1602419113 }}
6. ^{{cite journal | vauthors = Dombrowski Y, Peric M, Koglin S, Kammerbauer C, Göss C, Anz D, Simanski M, Gläser R, Harder J, Hornung V, Gallo RL, Ruzicka T, Besch R, Schauber J | title = Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions | journal = Science Translational Medicine | volume = 3 | issue = 82 | pages = 82ra38 | date = May 2011 | pmid = 21562230 | pmc = 3235683 | doi = 10.1126/scitranslmed.3002001 }}
7. ^{{cite journal | vauthors = Monteith AJ, Kang S, Scott E, Hillman K, Rajfur Z, Jacobson K, Costello MJ, Vilen BJ | title = Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 15 | pages = E2142-51 | date = April 2016 | pmid = 27035940 | doi = 10.1073/pnas.1513943113 }}

External links

  • {{UCSC gene info|AIM2}}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Landolfo S, Gariglio M, Gribaudo G, Lembo D | title = The Ifi 200 genes: an emerging family of IFN-inducible genes | journal = Biochimie | volume = 80 | issue = 8–9 | pages = 721–8 | year = 1999 | pmid = 9865494 | doi = 10.1016/S0300-9084(99)80025-X }}
  • {{cite journal | vauthors = Woerner SM, Kloor M, Schwitalle Y, Youmans H, von Knebel Doeberitz M, Gebert J, Dihlmann S | title = The putative tumor suppressor AIM2 is frequently affected by different genetic alterations in microsatellite unstable colon cancers | journal = Genes Chromosomes Cancer | volume = 46 | issue = 12 | pages = 1080–9 | year = 2007 | pmid = 17726700 | doi = 10.1002/gcc.20493 }}
  • {{cite journal | vauthors = Chen IF, Ou-Yang F, Hung JY, Liu JC, Wang H, Wang SC, Hou MF, Hortobagyi GN, Hung MC | title = AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model | journal = Mol. Cancer Ther. | volume = 5 | issue = 1 | pages = 1–7 | year = 2006 | pmid = 16432157 | doi = 10.1158/1535-7163.MCT-05-0310 }}
  • {{cite journal | vauthors = Cresswell KS, Clarke CJ, Jackson JT, Darcy PK, Trapani JA, Johnstone RW | title = Biochemical and growth regulatory activities of the HIN-200 family member and putative tumor suppressor protein, AIM2 | journal = Biochem. Biophys. Res. Commun. | volume = 326 | issue = 2 | pages = 417–24 | year = 2005 | pmid = 15582594 | doi = 10.1016/j.bbrc.2004.11.048 }}
  • {{cite journal | vauthors = Liu G, Yu JS, Zeng G, Yin D, Xie D, Black KL, Ying H | title = AIM-2: a novel tumor antigen is expressed and presented by human glioma cells | journal = J. Immunother. | volume = 27 | issue = 3 | pages = 220–6 | year = 2004 | pmid = 15076139 | doi = 10.1097/00002371-200405000-00006 }}
  • {{cite journal | vauthors = Choubey D, Walter S, Geng Y, Xin H | title = Cytoplasmic localization of the interferon-inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200-gene family | journal = FEBS Lett. | volume = 474 | issue = 1 | pages = 38–42 | year = 2000 | pmid = 10828447 | doi = 10.1016/S0014-5793(00)01571-4 }}
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