AhR-mediated, non-genomic modulation of IDO1 function.
The evolutionary process has conferred a dual – enzymic and signaling – function on the ancestral metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which has long been known for converting the essential amino acid tryptophan into neuroactive and immunoactive catabolites (kynurenines). In additi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00497/full |
| _version_ | 1798043987882278912 |
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| author | Maria Teresa Pallotta Francesca eFallarino Davide eMatino Antonio eMacchiarulo Ciriana eOrabona |
| author_facet | Maria Teresa Pallotta Francesca eFallarino Davide eMatino Antonio eMacchiarulo Ciriana eOrabona |
| author_sort | Maria Teresa Pallotta |
| collection | DOAJ |
| description | The evolutionary process has conferred a dual – enzymic and signaling – function on the ancestral metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which has long been known for converting the essential amino acid tryptophan into neuroactive and immunoactive catabolites (kynurenines). In addition to tryptophan catabolic activity, phosphorylated immunoreceptor tyrosine-based inhibitory motifs (ITIMs), present in the IDO1 protein, act as docking sites for different molecular partners, which activate positive (transcriptional) or negative (posttranslational) modulation of IDO1 protein. The ligand-operating transcription factor aryl hydrocarbon receptor (AhR) contributes to Ido1 transcription, and it can be operated by both exogenous as well as endogenous ligands, including L-kynurenine itself, the first byproduct of tryptophan catabolism. Ligand-bound AhR is also a component of an ubiquitin ligase complex, responsible for regulatory proteolysis of different target proteins. Because IDO1 half-life is controlled by the ubiquitin-proteasome system, we here discuss the possibility that AhR, in addition to enhancing Ido1 transcription, contributes to IDO1 regulation by a non-genomic mechanism affecting the protein’s half-life. |
| first_indexed | 2024-04-11T22:56:40Z |
| format | Article |
| id | doaj.art-d371e041282b43bfb301f6fb77d87b7a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T22:56:40Z |
| publishDate | 2014-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d371e041282b43bfb301f6fb77d87b7a2022-12-22T03:58:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-10-01510.3389/fimmu.2014.00497110529AhR-mediated, non-genomic modulation of IDO1 function.Maria Teresa Pallotta0Francesca eFallarino1Davide eMatino2Antonio eMacchiarulo3Ciriana eOrabona4University of PerugiaUniversity of PerugiaUniversity of PerugiaUniversity of PerugiaUniversity of PerugiaThe evolutionary process has conferred a dual – enzymic and signaling – function on the ancestral metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which has long been known for converting the essential amino acid tryptophan into neuroactive and immunoactive catabolites (kynurenines). In addition to tryptophan catabolic activity, phosphorylated immunoreceptor tyrosine-based inhibitory motifs (ITIMs), present in the IDO1 protein, act as docking sites for different molecular partners, which activate positive (transcriptional) or negative (posttranslational) modulation of IDO1 protein. The ligand-operating transcription factor aryl hydrocarbon receptor (AhR) contributes to Ido1 transcription, and it can be operated by both exogenous as well as endogenous ligands, including L-kynurenine itself, the first byproduct of tryptophan catabolism. Ligand-bound AhR is also a component of an ubiquitin ligase complex, responsible for regulatory proteolysis of different target proteins. Because IDO1 half-life is controlled by the ubiquitin-proteasome system, we here discuss the possibility that AhR, in addition to enhancing Ido1 transcription, contributes to IDO1 regulation by a non-genomic mechanism affecting the protein’s half-life.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00497/fullAhRdendritic cells.ImmunoregulationUbiquitin ligase complexITIML-kynurenine |
| spellingShingle | Maria Teresa Pallotta Francesca eFallarino Davide eMatino Antonio eMacchiarulo Ciriana eOrabona AhR-mediated, non-genomic modulation of IDO1 function. Frontiers in Immunology AhR dendritic cells. Immunoregulation Ubiquitin ligase complex ITIM L-kynurenine |
| title | AhR-mediated, non-genomic modulation of IDO1 function. |
| title_full | AhR-mediated, non-genomic modulation of IDO1 function. |
| title_fullStr | AhR-mediated, non-genomic modulation of IDO1 function. |
| title_full_unstemmed | AhR-mediated, non-genomic modulation of IDO1 function. |
| title_short | AhR-mediated, non-genomic modulation of IDO1 function. |
| title_sort | ahr mediated non genomic modulation of ido1 function |
| topic | AhR dendritic cells. Immunoregulation Ubiquitin ligase complex ITIM L-kynurenine |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00497/full |
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