Alternative titles; symbols
HGNC Approved Gene Symbol: AIF1
Cytogenetic location: 6p21.33 Genomic coordinates (GRCh38): 6:31,615,234-31,617,015 (from NCBI)
Autieri (1996) cloned a full-length cDNA of AIF1 (for allograft inflammatory factor-1) from a human peripheral blood lymphocyte cDNA library. The corresponding rat gene had been shown by differential display PCR to undergo increased expression in response to vascular injury incurred during balloon angioplasty. Sequence analysis revealed that AIF1 encodes a 143-amino acid polypeptide 4 amino acids shorter than that of rat Aif1; differences in this respect reside primarily at the C terminus. Amino acid motif analysis of AIF1 revealed a consensus EF-hand helix loop domain that is a conserved feature of calcium-binding proteins. Autieri (1996) showed that Aif1 expression is elevated 8- to 9-fold in the 3 days following balloon angioplasty. The author also demonstrated that the constitutive level of AIF1 mRNA in peripheral blood lymphocytes can be augmented by the mitogen phytohemagglutinin A (PHA). The author concluded that AIF1 represents a cytokine-inducible, tissue-specific, and highly conserved transcript transiently expressed in response to vascular trauma. Northern blot analysis revealed that AIF1 is expressed in a variety of human tissues, with highest expression in tissues of lymphoid origin, in particular, spleen, blood lymphocytes, and thymus.
Autieri and Agrawal (1998) identified IRT1 by stimulating vascular smooth muscle cells (VSMCs) with various cytokines. Northern blot analysis revealed wide but variable constitutive expression of a 1.3-kb IRT1 transcript in human tissues and in VSMCs stimulated with gamma-interferon (IFNG; 147570) but not with other cytokines or growth factors. IRT1 expression was downregulated in proliferating T cells. Expression of IRT1 was stimulated by balloon angioplasty in rat carotid arteries, possibly due to the presence of Ifng-producing T lymphocytes at the injury site. The predicted protein contains a leucine zipper motif, a hydrophobic region, a nuclear localization sequence, and 2 potential phosphorylation sites. Overexpression of IRT1 in VMSCs resulted in altered morphology and inhibition of cell growth.
Using in vitro binding and coimmunoprecipitation assays, Autieri et al. (2003) determined that AIF1 interacts with actin. In unstimulated VSMCs, AIF1 colocalized with F-actin, but translocated to lamellipodia upon PDGF (see 190040) stimulation. VSMCs stably transduced with AIF1 retrovirus migrated 2.6-fold more rapidly in response to PDGF than control cells. AIF1 colocalized with RAC1 (602048), and AIF1-transduced VSMCs showed a constitutive and enhanced activation of RAC1. Autieri et al. (2003) concluded that AIF1 binds and polymerizes F-actin and regulates RAC1 activity and VSMC migration.
The AIF1 gene resides in the tumor necrosis factor (TNF) cluster of genes located in the region represented by the human major histocompatibility complex (MHC) on 6p21.3 (Allcock et al., 2004).
Allcock, R. J. N., Windsor, L., Gut, I. G., Kucharzak, R., Sobre, L., Lechner, D., Garnier, J.-G., Baltic, S., Christiansen, F. T., Price, P. High-density SNP genotyping defines 17 distinct haplotypes of the TNF block in the Caucasian population: implications for haplotype tagging. Hum. Mutat. 24: 517-525, 2004. [PubMed: 15523649] [Full Text: https://doi.org/10.1002/humu.20100]
Autieri, M. V., Agrawal, N. IRT-1, a novel interferon-gamma-responsive transcript encoding a growth-suppressing basic leucine zipper protein. J. Biol. Chem. 273: 14731-14737, 1998. [PubMed: 9614071] [Full Text: https://doi.org/10.1074/jbc.273.24.14731]
Autieri, M. V., Kelemen, S. E., Wendt, K. W. AIF-1 is an actin-polymerizing and Rac1-activating protein that promotes vascular smooth muscle cell migration. Circ. Res. 92: 1107-1114, 2003. [PubMed: 12714565] [Full Text: https://doi.org/10.1161/01.RES.0000074000.03562.CC]
Autieri, M. V. cDNA cloning of human allograft inflammatory factor-1: tissue distribution, cytokine induction, and mRNA expression in injured rat carotid arteries. Biochem. Biophys. Res. Commun. 228: 29-37, 1996. [PubMed: 8912632] [Full Text: https://doi.org/10.1006/bbrc.1996.1612]