Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma.
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 identified a series of novel genes which are differentially 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 findings support the existence of a family of genes in this region similar to the well-characterized mouse Ifi200 gene family.
DeYoung
K L
KL
Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ray
M E
ME
Su
Y A
YA
Anzick
S L
SL
Johnstone
R W
RW
Trapani
J A
JA
Meltzer
P S
PS
Trent
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis*; D018922:HL-60 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data
D018076:DNA, Complementary; D007371:Interferon-gamma