Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma

Abstract

Chromosome 6-mediated suppression of tumorigenicity in malignant melanoma cell lines provides a model system to identify genes associated with the reversion of the tumorigenic phenotype. Using subtractive cDNA selection, we recently identi®ed a series of novel genes which are di erentially expressed in association with chromosome 6-mediated suppression. We now report the molecular characterization of a novel gene termed AIM2 for (Absent In Melanoma), which represents a 1485 bp cDNA. An open reading frame of 1032 base pairs, corresponding to 344 amino acid residues, is predicted. The predicted protein shares a conserved sequence domain of approximately 200 amino acids with known interferon-inducible genes of both human and mouse. We demonstrate that the AIM2 gene encodes a transcript of approximately 2 kb which is expressed in spleen, small intestine, and peripheral blood leukocytes. In addition, we have localized AIM2 to the long arm of human chromosome 1 (band q22) in a highly conserved region which also contains the known interferon-inducible genes IFI16 and MNDA. We have also demonstrated that, like IFI16 and MNDA, AIM2 is induced in HL60 cells by interferon gamma. Our ®ndings support the existence of a family of genes in this region similar to the well-characterized mouse I®200 gene family.

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

“…Absent in melanoma 2 (AIM2), an essential inflammasome functioning in human innate immune system, was originally isolated from human melanoma cells (DeYoung et al ., 1997). AIM2 is a member of the interferon‐inducible PYHIN (PYRIN and HIN domain‐containing) family proteins (also known as p200‐family proteins) and serves as the front line of defense against pathogen infection via caspase‐1 activation (Chuong et al ., 2016; Gray et al ., 2016; Man and Kanneganti, 2015; Rommereim and Subramanian, 2015).…”

Pyroptotic Neuronal Cell Death Mediated by the AIM2 Inflammasome

“…6 AIM2 is activated by viral, bacterial, and host ectopic dsDNA and induces cleavage of procaspase-1, maturation of IL-1b, and pyroptosis. 7 Although AIM2 is expressed in tissue outside the immune system, 8 its functional role in either the recognition of pathogenic DNA, or autoimmune reactions to host nucleic acids, has only been established in innate immune cells. It is unknown if AIM2 regulates the innate immune response to dsDNA in other cell types, such as neurons.…”

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

“…However, prior to its identification as a DNA sensor, a role for AIM2 in tumour suppression was proposed. Indeed AIM2 was actually first identified in tumour cells lines whose tumorigenicity is intentionally suppressed [27]. Others supported this idea that AIM2 is a tumour suppressor and this role has been noted in many systems [28].…”