Indoleamine 2,3-dioxygenase

Source: Wikipedia, the free encyclopedia.
IDO1
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000131203

ENSMUSG00000031551

UniProt

P14902

P28776

RefSeq (mRNA)

NM_002164

NM_008324
NM_001293690

RefSeq (protein)

NP_002155

NP_001280619
NP_032350

Location (UCSC)Chr 8: 39.9 – 39.93 MbChr 8: 25.07 – 25.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Indoleamine 2,3-dioxygenase
crystal structure of 4-phenylimidazole bound form of human indoleamine 2,3-dioxygenase
Identifiers
SymbolIDO
PfamPF01231
Pfam clanCL0380
InterProIPR000898
PROSITEPDOC00684
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Indoleamine 2,3-dioxygenase
Identifiers
ExPASy
NiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO

T-cell function and engage mechanisms of immune tolerance.[11] Emerging evidence suggests that IDO becomes activated during tumor development, helping malignant cells escape eradication by the immune system. Expression of IDO has been described in a number of types of cancer, such as acute myeloid leukemia, ovarian cancer or colorectal cancer. IDO is part of the malignant transformation process and plays a key role in suppressing the anti-tumor immune response in the body, so inhibiting it could increase the effect of chemotherapy as well as other immunotherapeutic protocols.[12][13][14] Furthermore, there is data implicating a role for IDO1 in the modulation of vascular tone in conditions of inflammation via a novel pathway involving singlet oxygen.[15]

Physiological function

Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway.

IDO is an important molecule in the mechanisms of tolerance and its physiological functions include the suppression of potentially dangerous

herpes simplex[19] or measles.[20]

One of the organs with high IDO expression is the placenta. In the 1990s, the immunosuppressive function of this enzyme was first described in mice due to the study of placental tryptophan metabolism. Thus, mammalian placenta, due to intensive tryptophan catabolism has the ability to suppress T cell activity, thereby contributing to its position of immunologically privileged tissue.[21]

Clinical significance

IDO is an

Tregs and myeloid-derived suppressor cells, and also supports angiogenesis.[12]

These mechanisms are crucial in the process of

carcinogenesis. IDO allows tumor cells to escape the immune system by two main mechanisms. The first mechanism is based on tryptophan depletion from the tumor microenvironment.[23] The second mechanism is based on the production of catabolic products called kynurenins, that are cytotoxic for T lymphocytes and NK cells.[24] Overexpression of human IDO (hIDO) is described in a variety of human tumor cell lineages and is often associated with poor prognosis.[25][26] Tumors with increased production of IDO include prostate, ovarian, lung or pancreatic cancer or acute myeloid leukemia.[27][28] Expression of IDO is under physiological conditions regulated by the Bin1 gene, which can be damaged by tumor transformation.[29]

Emerging clinical studies suggest that combination of IDO inhibitors with classical

radiotherapy could restore immune control and provide a therapeutic response to generally resistant tumors. Enzyme IDO used by tumors to escape immune surveillance is currently in focus of research and drug discovery efforts,[30] as well as efforts to understand if it could be used as a biomarker for prognosis.[31]

Inhibitors

COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity.[citation needed
]

indoximod
) is in clinical trials for various cancers.

Epacadostat (INCB24360), navoximod (GDC-0919), and linrodostat (BMS-986205) are potent inhibitors of the indoleamine 2,3-dioxygenase enzyme and are in clinical trials for various cancers.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131203 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031551 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 3877502
    .
  6. ^ "Entrez Gene: INDO indoleamine-pyrrole 2,3 dioxygenase".
  7. PMID 25477879
    .
  8. PMID 27547037
    .
  9. PMID 279015
    .
  10. PMID 291064
    .
  11. PMID 23103127
    .
  12. ^
    PMID 24711084
    .
  13. PMID 26839260
    .
  14. S2CID 10618102
    .
  15. S2CID 61156683
    .
  16. S2CID 4391121
    .
  17. PMID 29163470
    .
  18. PMID 9728563
    .
  19. PMID 14963171
    .
  20. PMID 15919929
    .
  21. PMID 9712583
    .
  22. PMID 26674411
    .
  23. PMID 10224276
    .
  24. PMID 12186838
    .
  25. ISSN 0531-5131
    .
  26. PMID 20350764
    .
  27. S2CID 10618102
    .
  28. PMID 25686005
    .
  29. S2CID 12338548
    .
  30. PMID 25686005
    .
  31. PMID 30134237
    .

External links
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