NT5E

Source: Wikipedia, the free encyclopedia.
NT5E
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_002526
NM_001204813

NM_011851

RefSeq (protein)

NP_001191742
NP_002517

NP_035981

Location (UCSC)Chr 6: 85.45 – 85.5 MbChr 9: 88.21 – 88.25 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the NT5E gene.[5] CD73 commonly serves to convert AMP to adenosine.[6]

Transcription factor binding sites

NT5E contains binding sites for

SP-1 and elements responsive to c-AMP , which can be found in c-AMP promoter parts. SMADs 2, 3, 4 and 5 and SP-1 are binding to the NT5E promoter in rats, as was proven in chromatin immunoprecipitation assays. Due to the fact, that the human and rat NT5E transcripts are 89% identical, human NT5E could be also regulated by SMAD proteins.[7]

Function

Ecto-5-prime-nucleotidase (5-prime-ribonucleotide phosphohydrolase; EC 3.1.3.5) catalyzes the conversion at neutral pH of purine 5-prime mononucleotides to nucleosides, the preferred substrate being

tibial arteries reducing circulation in the legs and the joints of the hands and feet causing pain.[9][10][11]

Immunosuppression

NT5E (CD73) is a surface

As a drug target

Some tumours have upregulation and overexpression of CD73 so it has been proposed as a drug target for cancer therapy.[14][15][16]

An anti-CD73 antibody CPI-006 has started early stage clinical trials as a treatment for advanced cancers.[17]

Systemic lupus erythematosus

Specialized immune cells such as myeloid-derived suppressor cells and regulatory T cells also mediate their effects via adenosine generated by local ectonucleotidase. In some cases of lupus patients, adequate T cell expression of CD73 is missing, which shows an impaired regulatory function of T cells.[18]

Cancer

NT5E can act as an immune inhibitory control molecule. Free adenosine generated by NT5E inhibits cellular immune responses and thereby promotes immune escape of tumor cells.

natural killer cell(NK). Thus, adenosine may inhibit the function of these immune cells. In addition, the tumor cells may also express adenosine A1 and A3 receptors associated with Gαi proteins, promoting both the migration and proliferation of tumor cells.[13][19][21] Especially due to its beneficial effects in mouse tumor model, anti-CD73 therapy is now a promising approach to cancer treatment in the future. CD73 inhibitor are currently being tested in clinical trials for the cancer treatment.[19]

miRNA

MicroRNA are small non-coding RNA molecules which regulate gene expression at posttranscriptional level via binding to mRNA. This leads to degradation of the target mRNA molecule or translational repression. In tumor cells the miRNA expression pattern often change and therefore affect the surface NT5E, which as result interfere the anti-tumor immune response.[22][23] For example, studies confirm the role of the miR30 family in NT5E regulation. Upon miR-30a-5p expression, NT5E expression was decreased.[13]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135318 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032420 - 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 2129526
    .
  6. , retrieved 2020-11-28
  7. .
  8. ^ "Entrez Gene: NT5E 5′-nucleotidase, ecto (CD73)".
  9. PMID 21288095
    .
  10. .
  11. ^ Online Mendelian Inheritance in Man (OMIM): 211800
  12. PMID 27665459
    .
  13. ^ .
  14. ^ Targeting adenosine for cancer immunotherapy 2018
  15. ^ Anti-CD73 in Cancer Immunotherapy: Awakening New Opportunities 2016
  16. S2CID 58767911
    .
  17. ^ Anti-CD73 antibody agent appears safe, shows promise in advanced cancers
  18. PMID 29942314
    .
  19. ^ .
  20. .
  21. .
  22. .
  23. .

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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