Abstract
Indoleamine 2,3-dioxygenase (IDO1, EC 1.13.11.52, Gene ID NM_002164.4) is coded by the INDO (or IDO-1) gene situated on chromosome 8p12 in humans. The enzyme is a 407-amino acid heme-containing cytoplasmic protein that catabolizes tryptophan into N-formylkynurenine via cleavage and oxidation of tryptophan’s pyrrole ring. The current form of IDO predominates in placental and marsupial mammals, whereas only less active prototypical IDO variants have been identified in chicken and fish genomes (Yuasa et al., Mol Evol 65:705–714, 2007). This adds credence to the important role IDO plays in the maintenance of placental pregnancy in mammals. In its normal physiologic role, IDO is important in modulating immune activation to antigenic challenges at mucosal surfaces in the digestive tract and lungs (Ciorba et al., J Immunol 184:3907–3916, 2010; Xu et al., Proc Natl Acad Sci U S A 105:6690–6695, 2008). The depletion of tryptophan in the tissue microenvironment by IDO exerts an antiproliferative effect on cancer cells and pathogens such as toxoplasmosis, trypanosomes, and chlamydia (Daubener and MacKenzie, Adv Exp Med Biol 467:517–524, 1999; Knubel et al., Faseb J 24:2689–2701, 2010). The gene is regulated by IFN-γ-responsive elements in its promoter region that bind activated STAT1, interferon regulatory factor-1 (IRF-1), and NF-kβ (Chon et al., J Biol Chem 271:17247–1752, 1996). IDO expression is detected in the brain, lungs, gut, kidneys, multiple tumor cell types, plasmacytoid dendritic cells (pDCs) within draining lymph nodes and the spleen, and human mesenchymal stem cells (Batista et al., Mol Imaging Biol 11:460–466, 2009; Gao et al., J Transl Med 7:71, 2009; Brandacher et al., Kidney Int 71:60–67, 2007; Munn et al., J Clin Invest 114:280–290, 2004; Uyttenhove et al., Nat Med 9:1269–1274, 2003; Ling et al., Cancer Res 74:1576–1587, 2014).
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Soliman, H.H. (2017). Indoleamine 2,3-dioxygenase. In: Marshall, J. (eds) Cancer Therapeutic Targets. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0717-2_134
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