Version 1
: Received: 23 September 2024 / Approved: 23 September 2024 / Online: 23 September 2024 (15:31:46 CEST)
How to cite:
Suvieri, C.; Belladonna, M. L.; Volpi, C. Indoleamine 2,3-Dioxygenase 2 (IDO2): The Protein That Lived Twice. Preprints2024, 2024091810. https://doi.org/10.20944/preprints202409.1810.v1
Suvieri, C.; Belladonna, M. L.; Volpi, C. Indoleamine 2,3-Dioxygenase 2 (IDO2): The Protein That Lived Twice. Preprints 2024, 2024091810. https://doi.org/10.20944/preprints202409.1810.v1
Suvieri, C.; Belladonna, M. L.; Volpi, C. Indoleamine 2,3-Dioxygenase 2 (IDO2): The Protein That Lived Twice. Preprints2024, 2024091810. https://doi.org/10.20944/preprints202409.1810.v1
APA Style
Suvieri, C., Belladonna, M. L., & Volpi, C. (2024). Indoleamine 2,3-Dioxygenase 2 (IDO2): The Protein That Lived Twice. Preprints. https://doi.org/10.20944/preprints202409.1810.v1
Chicago/Turabian Style
Suvieri, C., Maria Laura Belladonna and Claudia Volpi. 2024 "Indoleamine 2,3-Dioxygenase 2 (IDO2): The Protein That Lived Twice" Preprints. https://doi.org/10.20944/preprints202409.1810.v1
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2, originated from gene duplication before vertebrate diver-gence. While IDO1 has a well-defined role in immune regulation, the biological role of IDO2 remains unclear. Discovered in 2007, IDO2 is located near the IDO1 gene. Because of their high sequence similarity, IDO2 was initially thought to be a tryptophan (Trp)-degrading enzyme like IDO1. Differently from what expected, IDO2 displays extremely low catalytic activity toward Trp. Nevertheless, many studies, often contradictory, tried to demonstrate that IDO2 modulates immune responses by catabolizing Trp into kynurenine, a hypothesis un-convincing and, let’s say, linked to the first life of IDO2. Here, we review its “new life”, the one in which IDO2 has a functional role beyond Trp metabolism. The IDO2’s evolutionary persistence across species, despite be-ing almost inactive as an enzyme, suggests it has some relevant biological importance. IDO2 expression in human normal cells is poor, but significant in various cancers, with two prevalent SNPs. Overall, the com-parison of IDO2 to IDO1 as a Trp-degrading enzyme may have led to misunderstandings about IDO2’s true physiological and pathological roles. New insights suggest that IDO2 might function more as a signaling molecule, particularly in cancer contexts, and further studies could reveal its potential as a target for cancer therapy.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
